| 1. |
- Agardh, Emilie E, et al.
(författare)
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Explanations of socioeconomic differences in excess risk of type 2 diabetes in Swedish men and women.
- 2004
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 27:3, s. 716-21
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: We investigated to what extent socioeconomic differences in type 2 diabetes risk could be explained by established risk factors (obesity, physical inactivity, smoking, and heredity) and psychosocial factors (low decision latitude at work and low sense of coherence). RESEARCH DESIGN AND METHODS: This cross-sectional study comprised 3,128 healthy Swedish men and 4,821 women, aged 35-56 years, living in the Stockholm area. An oral glucose tolerance test identified 55 men and 52 women with type 2 diabetes. The relative contribution of established and psychosocial factors to socioeconomic differences in diabetes risk was assessed by comparing analyses with adjustment for different sets of these factors. RESULTS: The relative risks (RRs) for type 2 diabetes in middle and low socioeconomic groups in men were 2.4 (95% CI 1.0-5.3) and 2.9 (1.5-5.7), respectively, and in women 3.2 (1.5-6.6) and 2.7 (1.3-5.9), respectively. In men, the RRs decreased to 1.9 (0.8-4.4) and 2.1 (1.0-4.2) after adjustment for established risk factors; no further change was found when psychosocial factors were included. In women, the RRs changed to 2.4 (1.1-5.2) and 1.6 (0.7-3.8) by including established risk factors and to 2.3 (1.0-5.1) and 1.9 (0.8-4.3) by inclusion of psychosocial factors. After adjustment for both established and psychosocial factors, the RRs were 1.4 (0.6-3.6) and 1.0 (0.4-2.5), respectively. CONCLUSIONS: In men, the excess risk of type 2 diabetes was partly explained by established risk factors (36-42%), whereas psychosocial factors had no effect. In women, most of the socioeconomic differences in type 2 diabetes were explained by simultaneous adjustment for established risk factors and psychosocial factors (81-100%).
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| 2. |
- Agardh, Emilie E, et al.
(författare)
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Work stress and low sense of coherence is associated with type 2 diabetes in middle-aged Swedish women.
- 2003
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 26:3, s. 719-24
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The risk of type 2 diabetes is suggested to be increased for individuals exposed to stress. We analyzed the association of work stress by high demands, low decision latitude, and job strain (combination of high demands and low decision latitude) with type 2 diabetes. We also studied low sense of coherence (SOC) (a factor for successful coping with stressors) in association with type 2 diabetes. Finally, we investigated the combination of SOC and demands or SOC and decision latitude in association with the disease. RESEARCH DESIGN AND METHODS: This cross-sectional study recruited 4821 healthy Swedish women (aged 35-56 years) residing in five municipalities in the Stockholm area. An oral glucose tolerance test identified 52 women with type 2 diabetes. Relative risks (RRs) with 95% CIs were estimated in a logistic multiple regression analysis. RESULTS: No association was found between high demands and type 2 diabetes (RR 1.1 [CI 0.5-2.2]). Low decision latitude was associated with type 2 diabetes with a RR of 2.2 (1.0-4.8). The RR of type 2 diabetes with low SOC was 3.7 (1.2-11.2). The combination of low SOC and low decision latitude was associated with type 2 diabetes with a RR of 2.6 (1.2-5.7). Homeostasis model assessment revealed an association of 4.2 (1.2-15.0) between low SOC and insulin resistance. CONCLUSIONS: This study provided new evidence that stress factors such as low decision latitude at work and low SOC were associated with type 2 diabetes in middle-aged Swedish women.
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| 3. |
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| 4. |
- Ahrén, Bo, et al.
(författare)
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Inhibition of dipeptidyl peptidase IV improves metabolic control over a 4-week study period in type 2 diabetes.
- 2002
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 25:5, s. 869-75
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Glucagon-like peptide-1 (GLP-1) has been proposed as a new treatment modality for type 2 diabetes. To circumvent the drawback of the short half-life of GLP-1, inhibitors of the GLP-1-degrading enzyme dipeptidyl peptidase IV (DPP IV) have been examined. Such inhibitors improve glucose tolerance in insulin-resistant rats and mice. In this study, we examined the 4-week effect of 1-[[[2-[(5-cyanopyridin-2-yl)amino]ethyl]amino]acetyl]-2-cyano-(S)-pyrrolidine (NVP DPP728), a selective, orally active inhibitor of DPP IV, in subjects with diet-controlled type 2 diabetes in a placebo-controlled double-blind multicenter study.RESEARCH DESIGN AND METHODS: A total of 93 patients (61 men and 32 women), aged 64 +/- 9 years (means +/- SD) and with BMI 27.3 +/- 2.7 kg/m(2), entered the study. Fasting blood glucose was 8.5 +/- 1.5 mmol/l, and HbA(1c) was 7.4 +/- 0.7%. Before and after treatment with NVP DPP728 at 100 mg x 3 (n = 31) or 150 mg x 5 (n = 32) or placebo (n = 30), subjects underwent a 24-h study with standardized meals (total 2,000 kcal).RESULTS: Compared with placebo, NVP DPP728 at 100 mg t.i.d. reduced fasting glucose by 1.0 mmol/l (mean), prandial glucose excursions by 1.2 mmol/l, and mean 24-h glucose levels by 1.0 mmol/l (all P < 0.001). Similar reductions were seen in the 150-mg b.i.d. treatment group. Mean 24-h insulin was reduced by 26 pmol/l in both groups (P = 0.017 and P = 0.023). Although not an efficacy parameter foreseen in the study protocol, HbA(1c) was reduced to 6.9 +/- 0.7% in the combined active treatment groups (P < 0.001). Laboratory safety and tolerability was good in all groups.CONCLUSIONS: We conclude that inhibition of DPP IV is a feasible approach to the treatment of type 2 diabetes in the early stage of the disease.
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| 5. |
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| 6. |
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| 7. |
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| 8. |
- Hagander, Barbro, et al.
(författare)
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Dietary fiber decreases fasting blood glucose levels and plasma LDL concentration in noninsulin-dependent diabetes mellitus patients
- 1988
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Ingår i: American Journal of Clinical Nutrition. - 1938-3207. ; 47:5, s. 852-858
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Tidskriftsartikel (refereegranskat)abstract
- Realistic high-fiber and regular low-fiber diets were given for 8 wk each to noninsulin-dependent diabetes mellitus (NIDDM) patients whose diabetes was being controlled satisfactorily by diet alone. The purpose of the study was to evaluate the metabolic effects of dietary fiber without changing energy intake or proportions of protein, fat, and carbohydrates. The high-fiber diet induced lower fasting blood glucose levels (p less than 0.01) and decreased the ratio of low-density lipoproteins to high-density lipoproteins (p less than 0.025); no difference was found in HbA1c between the two diet periods. Continuous glucose monitoring also showed a difference in fasting glucose levels that remained after identical low-fiber test meals. The incremental glucose responses did not differ. The fasting and incremental postprandial levels of insulin, C-peptide, glucagon, and somatostatin did not change, whereas the mean triglyceride concentrations were lower after the high-fiber diet. The results suggest a beneficial effect of dietary fiber in the metabolic control of NIDDM.
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| 9. |
- Kuhl, Jeanette, et al.
(författare)
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Metabolomics as a tool to evaluate exercise-induced improvements in insulin sensitivity
- 2008
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Ingår i: Metabolomics. - : Springer Boston. - 1573-3882 .- 1573-3890. ; 4:3, s. 273-82
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Tidskriftsartikel (refereegranskat)abstract
- Exercise affects substrate utilisation and insulin sensitivity, which in turn improve blood glucose and lipid levels in subjects with type 2 diabetes (T2D). However, making long-lasting lifestyle-changes might be more realistic if the results were easier to record. Screening for biomarkers reflecting metabolic fitness could thus serve as a tool for maintained motivation. The aim of this study was to test the possibility that metabolomics can be used to identify individuals with improved insulin sensitivity as a result of increased physical activity. Healthy and diabetic subjects were investigated before and after 3 months of exercise to determine various metabolic parameters. Insulin sensitivity was determined by hyperinsulinemic euglycemic clamps and found to be improved in the diabetic men. Plasma was collected during the clamp and analyzed through GC/TOFMS. Healthy subjects could be distinguished from diabetics by means of low molecular-weight compounds (LMC) in plasma independently of gender or exercise, and exercise induced differences in LMC patterns both for healthy and T2D subjects. Forty-four significant metabolites were found to explain differences between LMC patterns obtained from trained and non-trained diabetics. Among these compounds, 17 could be annotated and 5 classified. Inositol-1-phosphate showed the highest correlation to insulin sensitivity in diabetic men, whereas an as yet unknown fatty acid correlated best with insulin sensitivity in women. Both metabolites were better correlated to insulin sensitivity than glucose. Finally, the finding that inostitol-1-phosphate negatively correlates with insulin sensitivity in diabetic men, was validated using samples obtained from a similar training study on diabetic men.
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| 10. |
- Ljungqvist, Olle, 1954-, et al.
(författare)
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Glucose infusion instead of preoperative fasting reduces postoperative insulin resistance
- 1994
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Ingår i: Journal of the American College of Surgeons. - 1072-7515 .- 1879-1190. ; , s. 329-336
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Tidskriftsartikel (refereegranskat)abstract
- In severe catabolic states, such as burn injury, sepsis and accidental injury, a state of marked insulin resistance is encountered. Insulin resistance is also present after elective surgical treatment, more pronounced with increasingly greater magnitude of operation performed. Results of recent animal experiments have shown that even short periods of food deprivation, reducing carbohydrate reserves, alter responses to stress. This notion resulted in our questioning the rationale of carbohydrate depletion associated with overnight preoperative fasting. Twelve patients undergoing elective open cholecystectomy were randomly given no infusion (control group) or 5 milligrams per kilogram per minute of glucose infusion (glucose group) during preoperative overnight fasting. Insulin sensitivity (M value, milligram per kilogram per minute) was determined using the hyperinsulinemic normoglycemic clamp (plasma insulin level, 65 microunits per milliliter and blood glucose level, 4.5 millimoles per liter) before and the first postoperative day. Preoperative insulin sensitivity was similar in the two groups. Postoperatively, M values decreased by 55±3 percent (control group) and by 32±5 percent (glucose group) (p<0.01). Plasma levels of insulin, c- peptide, glucagon, growth hormone, catecholamines and cortisol in connection with clamps were similar in both groups preoperatively and postoperatively. The present results indicate that active preoperative carbohydrate preservation may improve postoperative metabolism because postoperative occurrence of insulin resistance was reduced with preoperative glucose infusion.
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| 11. |
- Ma, Jun, et al.
(författare)
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Distribution of neuropeptide Y Leu7Pro polymorphism in patients with type 1 diabetes and diabetic nephropathy among Swedish and American populations.
- 2007
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Ingår i: Eur J Endocrinol. - 1479-683X. ; 157:5, s. 641-5
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The distribution of Leu7Pro polymorphism in the neuropeptide Y gene shows a geographical north to south gradient of decreasing frequency, suggesting that it may be a population-specific causal variant. This polymorphism is found to be associated with diabetic nephropathy (DN) and coronary heart disease in Finnish women with type 1 diabetes (T1D). The present study aims to evaluate the susceptibility of this polymorphism to the development of DN in two different populations. DESIGN: One sample set consists of 174 (females 98 and males 76) Swedish T1D patients with DN and 249 (females 132 and males 117) patients without DN. Another sample set includes 597 (females 356 and males 241) American T1D patients without DN and 577 (females 264 and males 313) patients with DN, who were descents of European Caucasians and were from the Genetics of Kidneys in Diabetes (GoKinD) Study. METHODS: Genotyping of Leu7Pro polymorphism was performed by dynamic allele-specific hybridization. RESULTS: The C allele frequencies of Leu7Pro polymorphism in T1D patients between Swedish and American GoKinD populations were significantly different (6.3 vs 4.0%; P=0.006). Particularly, the C allele frequency in Swedish female T1D patients with DN was significantly higher in comparison with T1D patients without DN (10.2 vs 4.2%; P=0.011, OR=2.614, 95% confidence intervals: 1.249-5.467). No significant association of this polymorphism with DN was observed in Swedish male T1D patients and the patients from GoKinD. CONCLUSIONS: The present study provides further evidence that Leu7Pro polymorphism confers the susceptibility to the development of DN in Swedish female T1D patients.
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| 12. |
- Ma, Jun, et al.
(författare)
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Genetic association analysis of the adiponectin polymorphisms in type 1 diabetes with and without diabetic nephropathy.
- 2007
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Ingår i: J Diabetes Complications. - : Elsevier BV. - 1056-8727. ; 21:1, s. 28-33
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Adiponectin [adipocyte C1q and collagen domain containing (ACDC)] is the most abundant adipose-specific protein. It is beneficial in that it improves insulin sensitivity and mitigates vascular damage, in addition to the possibility of it having anti-inflammatory properties. Clinical evidences demonstrate that serum adiponectin concentrations are increased in patients with type 1 diabetes (T1D) as well as in patients with microvascular complications. However, the genetic influence of the ACDC gene in T1D and diabetic microvascular complications is still unclear. The present study aims to evaluate the association of the ACDC genetic variation in T1D and diabetic nephropathy (DN). MATERIALS AND METHODS: Ten single nucleotide polymorphisms (SNPs) of the ACDC gene were genotyped in 432 T1D patients (of which, 196 had DN) and 187 nondiabetic control subjects, who were all Swedish Caucasians, by using dynamic allele specific hybridization. RESULTS: Single-marker association analysis demonstrated that SNPs +45G15G(T/G) and +276(G/T) were strongly associated with T1D [P=.002, OR=1.855 (1.266-2.717) and P=.001, OR=1.694 (1.337-2.147)]. Further analysis for haplotypes of these two SNPs indicated that one of the common haplotype (T_G) was strongly associated with T1D [P<.001, OR=1.769 (1.430-2.188)]. However, there was no significant difference in the allele frequencies of these two SNPs between the groups of T1D patients with nephropathy and the patients without nephropathy. CONCLUSIONS: The present study thus suggests that SNPs +45G15G(T/G) and +276(G/T) in the ACDC gene are associated with T1D but not with DN among Swedish Caucasians.
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| 13. |
- Mosén, Henrik, et al.
(författare)
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Impaired glucose-stimulated insulin secretion in the GK rat is associated with abnormalities in islet nitric oxide production.
- 2008
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Ingår i: Regulatory Peptides. - : Elsevier BV. - 1873-1686 .- 0167-0115. ; 151, s. 139-146
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Tidskriftsartikel (refereegranskat)abstract
- We investigated implications of nitric oxide (NO) derived from islet neuronal constitutive NO synthase (ncNOS) and inducible NOS (iNOS) on insulin secretory mechanisms in the mildly diabetic GK rat. Islets from GK rats and Wistar controls were analysed for ncNOS and iNOS by HPLC, immunoblotting and immunocytochemistry in relation to insulin secretion stimulated by glucose or l-arginine in vitro and in vivo. No obvious difference in ncNOS fluorescence in GK vs control islets was seen but freshly isolated GK islets displayed a marked iNOS expression and activity. After incubation at low glucose GK islets showed an abnormal increase in both iNOS and ncNOS activities. At high glucose the impaired glucose-stimulated insulin release was associated with an increased iNOS expression and activity and NOS inhibition dose-dependently amplified insulin secretion in both GK and control islets. This effect by NOS inhibition was also evident in depolarized islets at low glucose, where forskolin had a further amplifying effect in GK but not in control islets. NOS inhibition increased basal insulin release in perfused GK pancreata and amplified insulin release after glucose stimulation in both GK and control pancreata, almost abrogating the nadir separating first and second phase in controls. A defective insulin response to l-arginine was seen in GK rats in vitro and in vivo, being partially restored by NOS inhibition. The results suggest that increased islet NOS activities might contribute to the defective insulin response to glucose and l-arginine in the GK rat. Excessive iNOS expression and activity might be deleterious for the beta-cells over time.
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| 14. |
- Nygren, J, et al.
(författare)
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Disturbed anabolic hormonal patterns in burned patients : the relation to glucagon
- 1995
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Ingår i: Clinical Endocrinology. - : Wiley-Blackwell Publishing Inc.. - 0300-0664 .- 1365-2265. ; 43:4, s. 491-500
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Complex changes in the anabolic regulators of metabolism occur after major injury. We have studied the time course for IGF-I and IGFBP-1 after burn injury and their relations to circulating levels of other anabolic and catabolic hormones. The hormonal patterns during the onset of sepsis were also investigated. Patients. Eight patients (age 36 (6) years, mean (SEM)) with major burn injury (burn area 42 (6)%) were studied. The first 2 days since the burn were used for rehydration therapy (rehydration period), after which a complete total parenteral nutrition (TPN) period was initiated. Seven of the eight patients developed sepsis, confirmed with positive blood cultures, during the study period. Six of the eight survived. Measurements. The hormonal changes determined inthe morning during the first 7 days after the burn and from day 22 to 24 were investigated. The superimposed effects of sepsis were studied by normalizing all data to the day of positive blood cultures and clinical onset of sepsis. Results. On admission, plasma levels of glucagon, IGFBP-1 and GH were elevated while levels of IGF-I were low. During the first week after the burn, morning levels of glucagon and insulin increased while levels of GH and IGF-I decreased. GH levels were still elevated compared to healthy subjects. Despite the increase in insulin levels, IGFBP-1 remained elevated. Three weeks after the burn injury, IGF-I levels were increased but still markedly below normal, while IGFBP-1 levels remained unchanged. Persistent elevations of insulin levels were combined with reductions in glucagon levels. Admission levels of IGFBP-1 correlated to nitrogen loss (negative nitrogen balance) during the first 24 hours after the burn (r = 0.84, P < 0.05). A correlation between negative nitrogen balance and glucagon levels was found during the early catabolic period in the rehydration period (i.e. days 2-3, r = 0.84, P < 0.01). The relative change in IGFBP-1 levels in the rehydration period correlated to changes in glucagon levels (days 2-3 vs admission, r = 0.65, P < 0.05). The insulin/glucagon molar ratio correlated to the IGF-I/IGFBP-1 ratio during both the rehydration period (days 2-3, r = 0.77, P < 0.05) and the third week after the burn (r = 0.77, P < 0.05). During the most catabolic phase in the first week after the burn (TPN period) there was an inverse relation between IGF-I and IGFBP-1 levels (r = -0.83, P < 0.05). During the less catabolic third week after the burn, an inverse correlation was found between IGF-I and glucagon (r = -0.83, P < 0.05). Sepsis, superimposed upon the burn trauma, was associated with transient elevations in IGFBP-1 and reductions in insulin despite elevated levels of glucose and a further 50% increase in nitrogen losses. Conclusions. The present findings show that marked changes in important anabolic regulating factors occur after major burn injury. Uncoupling of the GH-IGF-I axis, and the attenuation of the inhibitory effects of insulin on IGFBP-1, both contribute to the reduction in IGF-I levels and bioavailability, factors which may play an important role in post injury metabolism. Furthermore, these data suggest that of the catabolic hormones (catecholamines, cortisol and glucagon), primarily glucagon seem to be involved in the modulation of IGF-I and IGFBP-1 levels following burn injury.
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| 15. |
- Nygren, Jonas O., et al.
(författare)
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Perioperative insulin and glucose infusion maintains normal insulin sensitivity after surgery
- 1998
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Ingår i: American Journal of Physiology. - : American Physiological Society. - 0002-9513 .- 2163-5773. ; 275:1 Part 1, s. E140-E148
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Tidskriftsartikel (refereegranskat)abstract
- Elective surgery was performed after overnight fasting, a routine that may affect the metabolic response to surgery. We investigated the effects of insulin and glucose infusions before and during surgery on postoperative substrate utilization and insulin sensitivity. Seven patients were given insulin and glucose infusions 3 h before and during surgery (insulin group), and a control group of six patients underwent surgery after fasting overnight. Insulin sensitivity and glucose kinetics (D-[6,6-2H2]glucose) were measured before and immediately after surgery using a hyperinsulinemic, normoglycemic clamp. Glucose infusion rates and whole body glucose disposal decreased after surgery in the control group (-40 and -29%, respectively), whereas no significant change was found in the insulingroup (+16 and +25%). Endogenous glucose production remained unchanged in both groups. Postoperative changes in cortisol, glucagon, fat oxidation, and free fatty acids were attenuated in the insulin group (vs. control). We conclude that perioperative insulin and glucose infusions minimize the endocrine stress response and normalize postoperative insulin sensitivity and substrate utilization.
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| 16. |
- Nygren, Jonas, et al.
(författare)
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Preoperative oral carbohydrate administration reduces postoperative insulin resistance
- 1998
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Ingår i: Clinical Nutrition. - : Elsevier. - 0261-5614 .- 1532-1983. ; 17:2, s. 65-71
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Tidskriftsartikel (refereegranskat)abstract
- Infusions of carbohydrates before surgery reduce postoperative insulin resistance. We investigated the effects of a carbohydrate drink, given shortly before surgery, on postoperative metabolism. Method: Insulin sensitivity, glucose turnover ([6,6, 2H2]-D-glucose) and substrate utilization were measured using hyperinsulinemic normoglycemic clamps and indirect calorimetry in two matched groups of patients before and after elective colorectal surgery. The drink group (n = 7) received 800 ml of an isoosmolar carbohydrate rich beverage the evening before the operation (100 g carbohydrates), as well as another 400 ml (50 g carbohydrates) 2 h before the initiation of anesthesia. The fasted group (n = 7) was operated after an overnight fast. Results: After surgery, energy expenditure increased in both groups. Endogenous glucose production was higher after surgery and the difference was significant during low insulin infusion rates in both groups (P < 0.05). The supressibility of endogenous glucose production by the two step insulin infusion was similar pre- and postoperatively in both groups. At the high insulin infusion rate postoperatively, whole body glucose disposal was more reduced in the fasted group (-49 ± 6% vs -26 ± 8%, P < 0.05 vs drink). Furthermore, during high insulin infusion rates, glucose oxidation decreased postoperatively only in the fasted group (P < 0.05) and postoperative levels of fat oxidation were greater in the fasted group (P < 0.05 vs drink). Only minor postoperative changes in cortisol and glucagon were found and no differences were found between the treatment groups. Conclusions: Patients given a carbohydrate drink shortly before elective colorectal surgery displayed less reduced insulin sensitivity after surgery as compared to patients who were operated after an overnight fast.
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| 17. |
- Nygren, Jonas, et al.
(författare)
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Site of insulin resistance after surgery: : the contribution of hypocaloric nutrition and bed rest.
- 1997
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Ingår i: Clinical Science. - : Portland Press. - 0143-5221 .- 1470-8736. ; 93:2, s. 137-146
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Tidskriftsartikel (refereegranskat)abstract
- Insulin resistance after surgery has been shown to be related to several important derangements in protein and fat metabolism. However, mechanisms of impaired glucose tolerance after surgery remain ill-defined. 2. Insulinsensitivity and glucose (6,62H2-glucose) were studied in seven before and after elective surgery (surgery group), by two step-hyperinsulinaemic (0.3 and 0.8 munits kg-1min-1), normoglycaemic (4.5 mmol/l) clamps. Six healthy subjects were studied, using the same protocol, before and after a similar period of bed rest and hypocaloric nutrition (fast/bed rest group) to delineate the effects of surgery per se. 3. Basal endogenous glucose production and whole-body glucose disposal was higher after surgery (P < 0.001), whereas no change was found after fast/bed rest. During glucose clamps, the glucose infusion rates required to maintain normoglycaemia and whole-body glucose disposal decreased (P < 0.001) after surgery, while endogenous glucose production increased (P < 0.001). In the control subjects, levels of endogenous glucose production remained unchanged after fast/bed rest. In contrast, glucose infusion rates and whole-body glucose disposal during glucose clamps also decreased after fast/bed rest (P < 0.01). However, the relative decrease in both these parameters was greater after surgery compared with after fast/bed rest (P < 0.01). 4. After surgery, energy expenditure and fat oxidation increased (P < 0.001), whereas glucose oxidation decreased (P < 0.05). No significant change was found in glucose utilization postoperatively. After fast/bed rest, no change was found in energy expenditure. However, fat oxidation increased (P < 0.01), whereas glucose oxidation and glucose utilization decreased (P < 0.05). 5. In conclusion, impaired glucose tolerance develops after surgery as a result of decreased insulin-stimulated whole-body glucose disposal as well as increased endogenous glucose release. Despite the increase in endogenous glucose production, the reduction in endogenous glucose production with each elevation of insulin was unaffected by surgery. Perioperative bed rest and/or hypocaloric nutrition contributed to the decrease in insulin-stimulated whole-body glucose disposal in the postoperative state, whereas these factors have no effects on endogenous glucose production.
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| 18. |
- Salehi, S Albert, et al.
(författare)
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Dysfunction of the islet lysosomal system conveys impairment of glucose-induced insulin release in the diabetic GK rat
- 1999
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Ingår i: Endocrinology. - 0013-7227. ; 140:7, s. 3045-3053
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Tidskriftsartikel (refereegranskat)abstract
- Accumulated evidence links an important signal involved in glucose-stimulated insulin release to the activation of the islet lysosomal glycogenolytic enzyme acid glucan-1,4-alpha-glucosidase. We have analyzed the function of the lysosomal system/lysosomal enzyme activities in pancreatic islets of young (6-8 weeks), spontaneously diabetic, GK (Goto-Kakizaki) rats and Wistar control rats in relation to glucose-induced insulin release. The insulin secretory response to glucose was markedly impaired in the GK rat, but was restored by the adenylate cyclase activator forskolin. Islet activities of classical lysosomal enzymes, e.g.. acid phosphatase, N-acetyl-beta-D-glucosaminidase, beta-glucuronidase, and cathepsin D, were reduced by 20-35% in the GK rat compared with those in Wistar controls. In contrast, the activities of the lysosomal alpha-glucosidehydrolases, i.e.. acid glucan-1,4-alpha-glucosidase and acid alpha-glucosidase, were increased by 40-50%. Neutral alpha-glucosidase (endoplasmic reticulum) was unaffected. Comparative analysis of liver tissue showed that lysosomal enzyme activities were of the same magnitude in GK and Wistar rats. Notably, in Wistar rats, the activities of acid glucan-1,4-alpha-glucosidase and acid alpha-glucosidase were approximately 15-fold higher in islets than in liver. Other lysosomal enzymes did not display such a difference. Normalization of glycemia in GK rats by phlorizin administered for 9 days did not influence either the lysosomal alpha-glucosidehydrolase activities or other lysosomal enzyme activities in GK islets. Finally, the pseudotetrasaccharide acarbose, which accumulates in the lysosomal system, inhibited acid glucan-1,4-alpha-glucosidase activity in parallel with its inhibitory action on glucose-induced insulin release in intact Wistar islets, whereas no effect was recorded for either parameter in intact GK islets. In contrast, acarbose inhibited the enzyme activity equally in islet homogenates from both GK and Wistar rats, showing that the catalytic activity of the enzyme itself in disrupted cells was unaffected. We propose that dysfunction of the islet lysosomal/vacuolar system is an important defect impairing the transduction mechanisms for glucose-induced insulin release in the GK rat.
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| 19. |
- Salehi, S Albert, et al.
(författare)
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Excessive islet NO generation in type 2 diabetic GK rats coincides with abnormal hormone secretion and is counteracted by GLP-1.
- 2008
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 3:5
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A distinctive feature of type 2 diabetes is inability of insulin-secreting beta-cells to properly respond to elevated glucose eventually leading to beta-cell failure. We have hypothesized that an abnormally increased NO production in the pancreatic islets might be an important factor in the pathogenesis of beta-cell dysfunction. PRINCIPAL FINDINGS: We show now that islets of type 2 spontaneous diabetes in GK rats display excessive NO generation associated with abnormal iNOS expression in insulin and glucagon cells, increased ncNOS activity, impaired glucose-stimulated insulin release, glucagon hypersecretion, and impaired glucose-induced glucagon suppression. Pharmacological blockade of islet NO production by the NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) greatly improved hormone secretion from GK islets suggesting islet NOS activity being an important target to inactivate for amelioration of islet cell function. The incretin hormone GLP-1, which is used in clinical practice suppressed iNOS and ncNOS expression and activity with almost full restoration of insulin release and partial restoration of glucagon release. GLP-1 suppression of iNOS expression was reversed by PKA inhibition but unaffected by the proteasome inhibitor MG132. Injection of glucose plus GLP-1 in the diabetic rats showed that GLP-1 amplified the insulin response but induced a transient increase and then a poor depression of glucagon. CONCLUSION: The results suggest that abnormally increased NO production within islet cells is a significant player in the pathogenesis of type 2 diabetes being counteracted by GLP-1 through PKA-dependent, nonproteasomal mechanisms.
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| 20. |
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| 21. |
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| 22. |
- Svensson, Annika M., et al.
(författare)
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Effects of glucagon-like peptide-1-(7-36)-amide on pancreatic islet and intestinal blood perfusion in Wistar rats and diabetic GK rats
- 2007
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Ingår i: Clinical Science. - 0143-5221 .- 1470-8736. ; 112:5-6, s. 345-351
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to evaluate the effects of GLP-1 [glucagon-like peptide-1-(7-36)-amide] on total pancreatic, islet and intestinal blood perfusion in spontaneously hyperglycaemic GK rats and normal Wistar rats using a microsphere technique. GK rats had hyperglycaemia and increased pancreatic and islet blood flow. Blood glucose concentrations were not affected when measured shortly (8 min) after GLP-1 administration in either GK or Wistar rats. GLP-1 had no effects on baseline pancreatic or islet blood flow in Wistar rats, but did prevent the blood flow increase normally seen following glucose administration to these animals. In GK rats, administration of GLP-1 decreased both pancreatic and islet blood flow. Glucose administration to the GK rats decreased pancreatic and islet blood flow. This decrease was not affected by pre-treatment with GLP-1. We conclude that administration of GLP-1 leads to a decrease in the augmented blood flow seen in islets of diabetic GK rats. The GLP-1-induced action on islet blood perfusion may modulate output of islet hormones and contribute to the antidiabetogenic effects of the drug in Type 2 diabetes (non-insulin-dependent diabetes).
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- Ware, James, et al.
(författare)
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Glucose, insulin and osmolar changes in rats sustaining different haemorrhage volumes.
- 1982
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Ingår i: Acta Physiologica Scandinavica. - : Almqvist & Wiksell. - 0001-6772 .- 1365-201X. ; 116:1, s. 31-36
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Tidskriftsartikel (refereegranskat)abstract
- Plasma glucose, osmolality and insulin have been investigated during hemorrhage in nonstarved rats. The rate of blood loss leading to hemorrhages of 44% and 55% of the estimated original blood volume determined the patterns of response. Substantial hyperglycemic hyperosmolality and insulin values appropriate for the raised levels of glucose were observed in the animals bleeding more rapidly. The slower rate of hemorrhage was associated with only moderate hyperglycemia and hyperosmolality, while the insulin values rose to very high levels, 45 times basal. It is postulated that altered glucose‐insulin metabolism in haemorrhage may have important consequences for fluid homeostasis, and the rate of bleeding is the fundamental factor steering this effect. © 1982 Scandinavian Physiological Society
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