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Influence of hyperinsulinemia and insulin resistance on in vivo β-cell function: their role in human β-cell dysfunction.

Abstract：

OBJECTIVE:Recent work has shown that insulin stimulates its own secretion in insulin-sensitive humans, suggesting that insulin resistance in the β-cell could cause β-cell dysfunction. We have tested whether insulin exposure and insulin sensitivity modulate β-cell function in subjects with normal glucose tolerance (NGT) and whether they contribute to dysglycemia in impaired glucose regulation (IGR). RESEARCH DESIGN AND METHODS:Insulin sensitivity (by euglycemic clamp), insulin-induced secretory response at isoglycemia (IISR) (as C-peptide percent change from basal during the clamp), glucose-induced secretory response (GISR) to an intravenous glucose bolus, and β-cell glucose sensitivity (β-GS) (by oral glucose tolerance test [OGTT] modeling) were measured in 1,151 NGT and 163 IGR subjects from the RISC (Relationship between Insulin Sensitivity and Cardiovascular Disease) study. RESULTS:In NGT, IISR was related to both insulin sensitivity and antecedent insulin exposure; GISR was related to insulin exposure. IISR was positively, if weakly, related to β-GS (r= 0.16, P < 0.0001). Both IISR (-23 [39] vs. -9 [2]%, median [interquartile range], P < 0.03) and β-GS (69 [47] vs. 118 [83] pmol ⋅ min(-1) ⋅ m(-2) ⋅ mmol(-1) ⋅ L, P < 0.0001) were decreased in IGR compared with NGT. Insulin sensitivity and β-GS were the major determinants of mean OGTT glucose in both NGT and IGR, with a minor role for IISR. In a multivariate logistic model, IGR was predicted by β-GS (odds ratio 4.84 [95% CI 2.89-8.09]) and insulin sensitivity (3.06 [2.19-4.27]) but not by IISR (1.11 [0.77-1.61]). CONCLUSIONS:Pre-exposure to physiological hyperinsulinemia stimulates insulin secretion to a degree that depends on insulin sensitivity. However, this phenomenon has limited impact on β-cell dysfunction and dysglycemia.

journal_name

Diabetes

journal_title

Diabetes

authors

Mari A,Tura A,Natali A,Anderwald C,Balkau B,Lalic N,Walker M,Ferrannini E,RISC Investigators.

doi

10.2337/db11-0827

subject

Has Abstract

pub_date

2011-12-01 00:00:00

pages

3141-7

issue

eissn

0012-1797

issn

1939-327X

pii

db11-0827

journal_volume

pub_type

临床试验,杂志文章

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Influence of hyperinsulinemia and insulin resistance on in vivo β-cell function: their role in human β-cell dysfunction.