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Insulin resistance alters islet morphology in nondiabetic humans.

ABSTRACT: Type 2 diabetes is characterized by poor glucose uptake in metabolic tissues and manifests when insulin secretion fails to cope with worsening insulin resistance. In addition to its effects on skeletal muscle, liver, and adipose tissue metabolism, it is evident that insulin resistance also affects pancreatic β-cells. To directly examine the alterations that occur in islet morphology as part of an adaptive mechanism to insulin resistance, we evaluated pancreas samples obtained during pancreatoduodenectomy from nondiabetic subjects who were insulin-resistant or insulin-sensitive. We also compared insulin sensitivity, insulin secretion, and incretin levels between the two groups. We report an increased islet size and an elevated number of β- and α-cells that resulted in an altered β-cell-to-α-cell area in the insulin- resistant group. Our data in this series of studies suggest that neogenesis from duct cells and transdifferentiation of α-cells are potential contributors to the β-cell compensatory response to insulin resistance in the absence of overt diabetes.

SUBMITTER: Mezza T

PROVIDER: S-EPMC3931397 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Insulin resistance alters islet morphology in nondiabetic humans.

Mezza Teresa T Muscogiuri Giovanna G Sorice Gian Pio GP Clemente Gennaro G Hu Jiang J Pontecorvi Alfredo A Holst Jens J JJ Giaccari Andrea A Kulkarni Rohit N RN

Diabetes 20131111 3

Type 2 diabetes is characterized by poor glucose uptake in metabolic tissues and manifests when insulin secretion fails to cope with worsening insulin resistance. In addition to its effects on skeletal muscle, liver, and adipose tissue metabolism, it is evident that insulin resistance also affects pancreatic β-cells. To directly examine the alterations that occur in islet morphology as part of an adaptive mechanism to insulin resistance, we evaluated pancreas samples obtained during pancreatoduo ...[more]

PMID: 24215793

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Project description:BackgroundLipoprotein insulin resistance (LPIR) score is a composite biomarker representative of atherogenic dyslipidemia characteristic of early insulin resistance. It is elevated in obesity and may provide information not captured in glycosylated hemoglobin and homeostatic model assessment for insulin resistance. While bariatric surgery reduces diabetes incidence and resolves metabolic syndrome, the effect of bariatric surgery on LPIR is untested.ObjectivesWe sought to assess the effects of Roux-en-Y gastric bypass and sleeve gastrectomy on LPIR in nondiabetic women with obesity.SettingNonsmoking, nondiabetic, premenopausal Hispanic women, age ≥18 years, undergoing Roux-en-Y gastric bypass or sleeve gastrectomy at Bellevue Hospital were recruited for a prospective observational study.MethodsAnthropometric measures and blood sampling were performed preoperatively and at 6 and 12 months postoperatively. LPIR was measured by nuclear magnetic resonance spectroscopy.ResultsAmong 53 women (Roux-en-Y gastric bypass, n = 22; sleeve gastrectomy, n = 31), mean age was 32 ± 7 years and body mass index 44.1 ± 6.4 kg/m2. LPIR was reduced by 35 ± 4% and 46 ± 4% at 6 and 12 months after surgery, respectively, with no difference by procedure. Twenty-seven of 53 patients met International Diabetes Federation criteria for metabolic syndrome preoperatively and had concomitant higher homeostatic model assessment for insulin resistance, glycosylated hemoglobin, nonhigh-density lipoprotein-cholesterol and LPIR. Twenty-five of 27 patients experienced resolution of metabolic syndrome postoperatively. Concordantly, the preoperative differences in homeostatic model assessment for insulin resistance, glycosylated hemoglobin, and nonhigh-density lipoprotein-cholesterol between those with and without metabolic syndrome resolved at 6 and 12 months. In contrast, patients with metabolic syndrome preoperatively exhibited greater LPIR scores at 6 and 12 months postoperatively.ConclusionThis is the first study to demonstrate improvement in insulin resistance, as measured by LPIR, after bariatric surgery with no difference by procedure. This measure, but not traditional markers, was persistently higher in patients with a preoperative metabolic syndrome diagnosis, despite resolution of the condition.

Project description:BackgroundInsulin resistance is linked to atherosclerotic cardiovascular diseases and stroke, whereas less is known about adipose tissue specific insulin resistance and outcomes after ischemic stroke. This study aimed to estimate the association between adipose tissue specific insulin resistance and prognosis of nondiabetic patients with ischemic stroke.MethodsPatients with ischemic stroke without a history of diabetes mellitus in the Third China National Stroke Registry were included. Adipose tissue specific insulin resistance index (Adipo-IR) was calculated by fasting serum insulin and free fatty acids and categorized into 5 groups according to the quintiles. Outcomes included stroke recurrence (ischemic or hemorrhagic), combined vascular events, all-cause death, and poor outcome (modified Rankin Scale, 3-6) at 12 months after stroke onset. We assessed the association between Adipo-IR and risk of prognosis by multivariable Cox/logistic regression models adjusted for potential covariates.ResultsAmong 2,222 patients, 69.0% were men with a mean age of 62.5 years. At 12 months, 185 (8.3%) patients had recurrent stroke, 193 (8.7%) had combined vascular events, 58 (2.6%) died, and 250 (11.5%) had a poor outcome. Compared with patients with the lowest quintile, patients with the second, third, fourth, fifth quintiles of the Adipo-IR were associated with an increased risk of stroke recurrence (hazard ratio [HR], 1.77; 95% CI, 1.04-3.03; P = 0.04; HR, 2.19; 95% CI, 1.30-3.68; P = 0.003; HR, 1.84; 95% CI, 1.06-3.21; P = 0.03; HR, 2.11; 95% CI, 1.20-3.71; P = 0.01, respectively) and marginally associated with an increased risk of combined vascular events ( HR, 1.60; 95%CI, 0.97-2.64; P = 0.07; HR, 1.91; 95% CI, 1.17-3.13; P = 0.01; HR, 1.62; 95% CI, 0.96-2.75; P = 0.07; HR, 1.80; 95% CI, 1.05-3.09; P = 0.03, respectively) at 12 months after adjustment for potential covariates. Adipo-IR was not associated with mortality and poor outcome at 12 months.ConclusionsThese findings suggest that adipose tissue specific insulin resistance is independently associated with recurrent stroke and combined vascular events after acute ischemic stroke in nondiabetic patients.

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Insulin resistance alters islet morphology in nondiabetic humans.

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Insulin resistance alters islet morphology in nondiabetic humans.

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