Different contributions of insulin resistance and beta‐cell dysfunction in overweight Israeli Arabs with IFG and IGT

Abdul‐Ghani, Muhammad; Sabbah, Muhammad; Kher, Joseph; Minuchin, Oscar; Vardi, Pnina

doi:10.1002/dmrr.595

Cited by 38 publications

(24 citation statements)

References 25 publications

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“…As HOMA-IR and HOMA-B were only surrogate measures of insulin sensitivity and insulin secretion, further investigations are warranted. IR and decreased insulin secretion are the major factors contributing to the deterioration of glucose metabolism [14,15]. Elderly individuals are apparently able to maintain normal glucose tolerance by secreting more insulin to overcome the IR [16].…”

Section: Discussionmentioning

confidence: 99%

Does abnormal insulin action or insulin secretion explain the increase in prevalence of impaired glucose metabolism with age in populations of different ethnicities?

Feng

Qiao

Tuomilehto

et al. 2010

Diabetes Metabolism Res

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Section: Discussionmentioning

confidence: 99%

Does abnormal insulin action or insulin secretion explain the increase in prevalence of impaired glucose metabolism with age in populations of different ethnicities?

Feng

Qiao

Tuomilehto

et al. 2010

Diabetes Metabolism Res

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“…Our approach to study insulin sensitivity using the FSIGT-derived S i at 24 h post-LPS is limited in that we cannot differentiate various contributions of changes in hepatic and peripheral insulin sensitivity versus the total body change and cannot define the kinetics of the development and resolution of IR. However, we utilized the FSIGT S i as a sensitive measure of peripheral IR and combined this with the HOMA-IR that correlates best with measures of hepatic insulin sensitivity (24). Furthermore, FSIGT enabled examination of whether pancreatic ␤-cell function changes during inflammation-induced IR, while the hyperinsulinemic-eugylemic clamp does not.…”

Section: Insulinmentioning

confidence: 99%

Experimental Endotoxemia Induces Adipose Inflammation and Insulin Resistance in Humans

et al. 2009

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OBJECTIVE-An emerging model of metabolic syndrome and type 2 diabetes is of adipose dysfunction with leukocyte recruitment into adipose leading to chronic inflammation and insulin resistance (IR). This study sought to explore potential mechanisms of inflammatory-induced IR in humans with a focus on adipose tissue. RESEARCH DESIGN AND METHODS-We performed a 60-h endotoxemia protocol (3 ng/kg intravenous bolus) in healthy adults (n ϭ 20, 50% male, 80% Caucasian, aged 27.3 Ϯ 4.8 years). Before and after endotoxin, whole-blood sampling, subcutaneous adipose biopsies, and frequently sampled intravenous glucose tolerance (FSIGT) testing were performed. The primary outcome was the FSIGT insulin sensitivity index (S i ). Secondary measures included inflammatory and metabolic markers and whole-blood and adipose mRNA and protein expression. RESULTS-Endotoxemia induced systemic IR as demonstratedby a 35% decrease in S i (3.17 Ϯ 1.66 to 2.06 Ϯ 0.73 ϫ 10 Ϫ4 [U ⅐ ml Ϫ1 ⅐ min Ϫ1 ], P Ͻ 0.005), while there was no effect on pancreatic ␤-cell function. In adipose, endotoxemia suppressed insulin receptor substrate-1 and markedly induced suppressor of cytokine signaling proteins (1 and 3) coincident with local activation of innate (interleukin-6, tumor necrosis factor) and adaptive (monocyte chemoattractant protein-1 and CXCL10 chemokines) inflammation. These changes are known to attenuate insulin receptor signaling in model systems.CONCLUSIONS-We demonstrate, for the first time in humans, that acute inflammation induces systemic IR following modulation of specific adipose inflammatory and insulin signaling pathways. It also provides a rationale for focused mechanistic studies and a model for human proof-of-concept trials of novel therapeutics targeting adipose inflammation in IR and related consequences in humans.

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“…8,[10][11][12][13][14] In contrast, insulin sensitivity has been shown to be lower in both IFG and IGT subjects when estimated based on an oral glucose tolerance test (OGTT) or homeostasis model assessment for insulin resistance (HOMA IR ). [15][16][17] The underlying mechanisms for impairments in insulin sensitivity in subjects with IGM are not yet fully understood. Skeletal muscle and adipose tissue are important organs in regulating fatty acid (FA) metabolism.…”

Section: Introductionmentioning

confidence: 99%

Impaired insulin sensitivity is accompanied by disturbances in skeletal muscle fatty acid handling in subjects with impaired glucose metabolism

et al. 2011

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Objective: To determine insulin sensitivity and skeletal muscle fatty acid (FA) handling at baseline and after a high-fat mixed meal in impaired fasting glucose (IFG), impaired glucose tolerance (IGT), IFG/IGT and normal glucose tolerance (NGT) subjects. Design: In this multi-center study, insulin sensitivity and b-cell function were assessed (n ¼ 102), using a euglycemichyperinsulinemic and hyperglycemic clamp with additional arginine stimulation and a 75 g oral glucose tolerance test. Fasting and postprandial skeletal muscle FA handling was examined in a substudy using the forearm balance technique (n ¼ 35). Subjects: A total of 102 subjects with IFG (n ¼ 48), IGT (n ¼ 12), IFG/IGT (n ¼ 26) and NGT (n ¼ 16). Results: IFG, IGT and IFG/IGT subjects had lower insulin sensitivity with no differences between groups, and lower impaired b-cell function compared with NGT controls. The early postprandial increase in triacylglycerol (TAG) concentration was higher (iAUC 0À2 h IFG: 238.4 ± 26.5, IGT: 234.0 ± 41.0 and NGT: 82.6 ± 13.8 mmol l À1 min À1 , both Po0.05) and early TAG extraction was increased (AUC 0À2 h IFG: 56.8±9.0, IGT: 52.2±12.0 and NGT: 3.8±15.4 nmol Á 100 ml À1 min À1 , Po0.05 and P ¼ 0.057, respectively) in both IFG and IGT subjects. Conclusion: IFG, IGT and IFG/IGT subjects have lower insulin sensitivity and impaired b-cell function compared with age-and BMI-matched NGT controls. The increased postprandial TAG response and higher muscle TAG extraction in both IFG and IGT compared with NGT may lead to ectopic fat accumulation in the skeletal muscle, thereby contributing to insulin resistance.

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Different contributions of insulin resistance and beta‐cell dysfunction in overweight Israeli Arabs with IFG and IGT

Cited by 38 publications

References 25 publications

Does abnormal insulin action or insulin secretion explain the increase in prevalence of impaired glucose metabolism with age in populations of different ethnicities?

Does abnormal insulin action or insulin secretion explain the increase in prevalence of impaired glucose metabolism with age in populations of different ethnicities?

Experimental Endotoxemia Induces Adipose Inflammation and Insulin Resistance in Humans

Impaired insulin sensitivity is accompanied by disturbances in skeletal muscle fatty acid handling in subjects with impaired glucose metabolism

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