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- Axelsson, T., et al.
(författare)
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Nicotine infusion acutely impairs insulin sensitivity in type 2 diabetic patients but not in healthy subjects
- 2001
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Ingår i: J Intern Med. - 0954-6820. ; 249:6, s. 539-44
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The aim of this study was to examine if an acute nicotine infusion alters insulin sensitivity to a similar degree in type 2 diabetic patients as in healthy control subjects. DESIGN: . Double-blind, cross-over, placebo-controlled, randomized experimental study. Nicotine 0.3 microg kg-1 min(-1) or NaCl was infused (2 h) during a euglycaemic hyperinsulinaemic clamp (4 h) to assess insulin sensitivity. SETTING: University research laboratory. SUBJECTS: Six male and female type 2 diabetic patients [DM2; age 54 +/- 10 (mean +/- SD) years; body mass index (BMI) 25.6 +/- 2.9 kg m(-2)] treated with diet or one oral hypoglycaemic agent and six age- and BMI-matched control subjects (Ctr). MAIN OUTCOME MEASURE: Insulin sensitivity (rate of glucose infusion per kg fat free body mass and minute), nicotine and free fatty acid (FFA) levels, pulse rate and blood pressure. RESULTS: The infusions produced similar nicotine levels in both groups. In the absence of nicotine, DM2 were more insulin resistant than Ctr (6.7 +/- 0.4 vs. 10.9 +/- 0.3 mg kg-1 LBM min(-1), respectively; P < 0.0001). This insulin resistance was further aggravated by the nicotine infusion in DM2 but not in Ctr (4.6 +/- 0.3 vs. 10.9 +/- 0.3 mg kg(-1) LBM min(-1); P < 0.0001). Only minor differences were seen in FFA levels, pulse rates and blood pressure. CONCLUSIONS: At this low infusion rate, nicotine aggravated the insulin resistance in DM2 but not in Ctr. This finding may be because of the (dysmetabolic) diabetic state per se or to an increased sensitivity to environmental factors associated with a genetic predisposition for type 2 diabetes. These results show that diabetic subjects are particularly susceptible to the detrimental effects of nicotine.
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| 2. |
- Jansson, Per-Anders, 1961, et al.
(författare)
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Endocrine abnormalities in healthy first-degree relatives of type 2 diabetes patients--potential role of steroid hormones and leptin in the development of insulin resistance.
- 2002
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Ingår i: European journal of clinical investigation. - : Wiley. - 0014-2972 .- 1365-2362. ; 32:3, s. 172-8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: First-degree relatives of type 2 diabetes patients are at risk of developing diabetes and they display several metabolic and hormonal perturbations. The interplay between insulin resistance, steroid hormones and circulating leptin is, however, still not fully explored in this group. DESIGN: Thirty-three healthy first-degree relatives of type 2 diabetic patients (relatives; M/F 19/14) were compared to 33 healthy subjects without a family history of diabetes (controls) and the groups were matched for gender, age and body mass index (BMI). We performed euglycaemic hyperinsulinaemic clamps and blood was sampled for hormone analyses. RESULTS: Relatives exhibited decreased insulin sensitivity (index of metabolic clearance rate of glucose; MCRI) but when genders were analysed separately, this difference was significant only in males (11.3 +/- 1.3 vs. 15.0 +/- 1.5 units, means +/- SEM, P = 0.030). In male relatives morning cortisol and testosterone levels were lower, whereas leptin was higher than in male controls (P = 0.018, 0.008 and 0.063, respectively). In male relatives plasma testosterone levels were significantly associated with insulin sensitivity (r = 0.48, P = 0.040). Circulating leptin levels were inversely correlated with insulin sensitivity in all subject groups (r-values -0.49 to -0.66; P < 0.05, except in female control subjects P = 0.063). These associations were present also when age and BMI or waist:hip ratio were included in stepwise multiple regression analyses. CONCLUSION: Male subjects genetically predisposed for type 2 diabetes display several endocrine abnormalities including leptin, cortisol and testosterone levels. Dysregulation of these hormones may be important in the development of insulin resistance and type 2 diabetes.
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| 3. |
- Smith, Ulf, 1943, et al.
(författare)
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Insulin signaling and action in fat cells: associations with insulin resistance and type 2 diabetes.
- 1999
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Ingår i: Annals of the New York Academy of Sciences. - 0077-8923. ; 892, s. 119-26
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Forskningsöversikt (refereegranskat)abstract
- Adipose tissue only accounts for a relatively small proportion (< 10%) of the peripheral glucose utilization in response to insulin. However, the fat cells may still play an important role in insulin resistance and Syndrome X through, for instance, its endocrine functions (production of leptin, TNF alpha, PAI-1, etc.) and involvement in lipid metabolism (FFA release and hydrolysis of triglycerides). The fat cells are also highly sensitive to insulin and may thus be used to elucidate molecular mechanisms for insulin resistance in man. Examinations of the intracellular signaling mechanisms for insulin in fat cells from individuals with Type 2 diabetes revealed markedly lower insulin-stimulated PI3-kinase activity. This was due to a pronounced reduction in the cellular expression of the docking protein, IRS 1, whereas expression of IRS 2 was normal. However, IRS 2-associated PI3-kinase activity was only approximately one-third of that found to be associated with IRS 1 in normal cells. Downstream activation and serine phosphorylation of PKB/Akt by insulin were also markedly reduced in Type 2 diabetes. Furthermore, the dose-response curve for this effect of insulin was similar to that for glucose transport in both normal and Type 2 diabetic cells. Thus, these data show that both PI3-kinase and PKB activation by insulin are markedly reduced in Type 2 diabetes. We also examined whether an attenuated activation of PI3-kinase by insulin can be seen in non-diabetic insulin-resistant states. Approximately 30% of healthy subjects with at least two first-degree relatives with Type 2 diabetes exhibited perturbations in IRS-1 expression and signaling. These individuals were characterized by insulin resistance as well as other markers of Syndrome X. Thus, impaired IRS-1 expression and downstream signaling events in fat cells in response to insulin are associated with insulin resistance and Syndrome X.
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