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- Abdelgadir, M, et al.
(författare)
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Reduced leptin concentrations in subjects with type 2 diabetes mellitus in Sudan.
- 2002
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Ingår i: Metabolism, Clinical and Experimental. - : Elsevier BV. - 1532-8600. ; 51:3, s. 304-306
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Tidskriftsartikel (refereegranskat)abstract
- Differences have been observed in the relationship between leptin and metabolic perturbations in glucose homeostasis. Because no information is available from indigenous African populations with diabetes, the purpose of this study was to investigate the possible associations between leptin and different clinical and biochemical characteristics of a large group of subjects with type 2 diabetes mellitus in Sudan. A total of 104 (45 men and 59 women) consecutive type 2 diabetes patients and 75 control subjects (34 men and 41 women) were studied. The body mass index (BMI), blood glucose, serum insulin, and proinsulin were measured and related to serum leptin concentrations. Leptin was higher in females than in males and correlated significantly to BMI. The main novel finding was that serum leptin was significantly lower in diabetic subjects compared with controls in both females (P =.0001) and males (P =.019), although BMI did not differ between diabetic and nondiabetic subjects. Diabetic subjects treated with sulphonylurea (n = 81) had lower BMI than those treated with diet alone or other hypoglycemic drugs (n = 23) (P =.0017), but there was no difference in leptin levels between the 2 groups after adjustment for BMI (P =.87). In diabetic subjects, serum leptin correlated positively with the homeostatic assessment (HOMA) of both beta-cell function (P =.018) and insulin resistance (P =.038), whereas in control subjects, leptin correlated with insulin resistance (P =.0016), but not with beta-cell function. Diabetic subjects had higher proinsulin levels (P =.0031) and higher proinsulin to insulin ratio (P =.0003) than nondiabetic subjects. In univariate analysis, proinsulin showed a weak correlation to leptin (P =.049). In conclusion, we show in a large cohort of Sudanese subjects with type 2 diabetes that circulating leptin levels are lower in diabetic subjectss than in controls of similar age and BMI. The lower serum leptin in diabetic subjects may be a consequence of differences in fat distribution.
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- Agardh, Carl-David, et al.
(författare)
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Long-standing hyperglycemia in C57BL/6J mice does not affect retinal glutathione levels or endothelial/pericyte ratio in retinal capillaries
- 2000
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Ingår i: Journal of Diabetes and its Complications. - 1873-460X. ; 14:3, s. 146-153
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Tidskriftsartikel (refereegranskat)abstract
- Free radicals have been suggested to play a role in the development of diabetic retinopathy. The aim of the present study was to examine whether the metabolic perturbations caused by high-fat feeding of two strains of mice, the C57BL6/J mice and the NMRI mice, interfere with one of the free radical enzyme defense systems in the retina, i. e., glutathione (GSH), and whether morphological changes occur in the retinal vessels. C57BL/6J mice and NMRI mice were fed a high-fat diet (55%) for 18 months. High-fat fed mice of both strains developed overweight, hyperinsulinemia, and hyperlipidemia. In addition, the high-fat fed C57BL/6J mice also developed sustained hyperglycemia for at least 15 months. The C57BL/6J mice had lower retinal GSH levels than the NMRI mice, both when given a normal diet (29.6+/-1.2 vs. 37.1+/-1.4 nmol/mg protein; p<0.01) and when given a high-fat diet (27.0+/-1.6 vs. 34.7+/-2.6 nmol/mg protein; p<0.05). Despite the long-standing hyperglycemia, hyperinsulinemia and hyperlipidemia in the C57BL/6J mice, high-fat feeding did not cause any changes in the retinal tissue levels of GSH (27.0+/-1.6 vs. 29. 6+/-1.2 nmol/mg protein) or cysteine (7.61+/-0.63 vs. 6.80+/-0.59 nmol/mg protein). Similarly, high-fat feeding did not affect retinal GSH or cysteine levels in NMRI mice. No light microscopical retinal vessel changes were seen, either in C57BL/6J or in NMRI mice. The study therefore shows that long-standing metabolic perturbations induced by dietary obesity do not induce signs of retinopathy in two different strains of mice. Further studies are needed to explore whether this is explained by increased expression of protecting systems making these strains of mice resistant to effects of oxidative stress.
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- Ahrén, Bo, et al.
(författare)
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Characterization of GLP-1 effects on beta-cell function after meal ingestion in humans.
- 2003
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 26:10, s. 2860-2864
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE—Glucagon-like peptide 1 (GLP-1) is an incretin that augments insulin secretion after meal intake and is developed for treatment of type 2 diabetes. As a novel therapeutic agent, characteristics of its β-cell effects are important to establish. Previously, β-cell effects of GLP-1 have been characterized in humans during graded intravenous infusions of glucose, whereas its effects after more physiological stimuli, like meal intake, are not known. RESEARCH DESIGN AND METHODS—Eight women (aged 69 years, fasting glucose 3.7–10.3 mmol/l, BMI 22.4–43.9 kg/m2) who had fasted overnight were served a breakfast (450 kcal) with intravenous infusion of saline or synthetic GLP-1 (0.75 pmol · kg–1 · min–1), and β-cell function was evaluated by estimating the relationship between glucose concentration and insulin secretion (calculated by deconvolution of C-peptide data). RESULTS—GLP-1 markedly augmented insulin secretion, despite lower glucose. Total insulin secretion was 29.7 ± 4.2 nmol/m2 with GLP-1 versus 21.0 ± 1.6 nmol/m2 with saline (P = 0.048). GLP-1 increased the dose-response relationship between glucose concentration and insulin secretion (70 ± 26 with GLP-1 versus 38 ± 16 pmol insulin · min−1 · m2 · mmol−1 glucose · l without, P = 0.037) and augmented the potentiation factor that modulates the dose response (2.71 ± 0.42 with GLP-1 versus 0.97 ± 0.17 without, P = 0.005). The potentiation factor correlated to GLP-1 concentration (r = 0.53, P < 0.001); a 10-fold increase in GLP-1 levels produced a twofold increase in the potentiation factor. These effects of GLP-1 did not correlate with fasting glucose levels or BMI. CONCLUSIONS—Administration of GLP-1 along with ingestion of a meal augments insulin secretion in humans by a dose-dependent potentiation of the dose-response relationship between plasma glucose and insulin secretion.
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- Ahrén, Bo, et al.
(författare)
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Differential impairment of glucagon responses to hypoglycemia, neuroglycopenia, arginine, and carbachol in alloxan-diabetic mice.
- 2002
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Ingår i: Metabolism, Clinical and Experimental. - : Elsevier BV. - 1532-8600. ; 51:1, s. 12-19
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Tidskriftsartikel (refereegranskat)abstract
- To gain insight into the mechanisms responsible for the loss of the glucagon response to insulin-induced hypoglycemia in type 1 diabetes, glucagon responses to 4 different stimuli were examined over 3 months of diabetes in alloxan-treated mice. At 1, 6, and 12 weeks after alloxan (60 mg/kg), phloridzin (0.1 g/kg) was administered to overnight fasted diabetic mice to match the glucose levels of those in nondiabetic control mice before administration of the acute stimuli. Despite the elevation of baseline glucagon levels produced by the phloridzin treatment, the glucagon responses to insulin (2 U/kg intraperitoneally [IP])-induced hypoglycemia was not impaired at 1 week. However, the response was reduced by greater than 60% after 6 and 12 weeks of diabetes (P <.05). In contrast, the glucagon response to arginine (0.25 g/kg intravenously [IV]) was not reduced after 1, 6, or 12 weeks of diabetes, ruling out a generalized impairment of the A-cell responses. The glucagon response to the neuroglucopenic agent, 2-deoxyglucose (2-DG; 500 mg/kg IV) was impaired, like that to insulin-induced hypoglycemia, after 6 and 12 weeks of diabetes (P <.05), suggesting that supersensitivity to the potential inhibitory effects of exogenous insulin is not the mechanism responsible for the impairment. Finally, the glucagon response to the cholinergic agonist, carbachol (0.53 micromol/kg IV), was not impaired in the diabetic animals, arguing against a defect in the A-cell's responsiveness to autonomic stimulation. The data suggest that the impairment of the glucagon response to insulin-induced hypoglycemia in alloxan diabetic mice is not due to a generalized impairment of A-cell responsiveness, to desensitization by a suppressive action of insulin, or to impairment of the A-cell response to autonomic stimuli. The remaining mechanisms which are likely to explain the late loss of the glucagon response to insulin-induced hypoglycemia include (1) a defect in the A-cell recognition of glucopenic stimuli, or (2) a defect in the autonomic inputs to the A cell that are known to be activated by glucopenic stimuli.
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- Ahrén, Bo
(författare)
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GLP-1 and extra-islet effects.
- 2004
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Ingår i: Hormone and Metabolic Research. - : Georg Thieme Verlag KG. - 1439-4286 .- 0018-5043. ; 36:11-12, s. 842-845
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