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Reduced β-cell function contributes to impaired glucose tolerance in dogs made obese by high-fat feeding

Published on Oct 1, 1999in American Journal of Physiology-endocrinology and Metabolism4.125
· DOI :10.1152/ajpendo.1999.277.4.E659
Karl J. Kaiyala20
Estimated H-index: 20
,
Ronald L. Prigeon31
Estimated H-index: 31
(UW: University of Washington)
+ 3 AuthorsMichael W. Schwartz106
Estimated H-index: 106
(UW: University of Washington)
Abstract
The ability to increase β-cell function in the face of reduced insulin sensitivity is essential for normal glucose tolerance. Because high-fat feeding reduces both insulin sensitivity and glucose tolerance, we hypothesized that it also reduces β-cell compensation. To test this hypothesis, we used intravenous glucose tolerance testing with minimal model analysis to measure glucose tolerance (K g), insulin sensitivity (SI), and the acute insulin response to glucose (AIRg) in nine dogs fed a chow diet and again after 7 wk of high-fat feeding. Additionally, we measured the effect of consuming each diet on 24-h profiles of insulin and glucose. After high-fat feeding, SI decreased by 57% (P = 0.003) but AIRg was unchanged. This absence of β-cell compensation to insulin resistance contributed to a 41% reduction of K g(P = 0.003) and abolished the normal hyperbolic relationship between AIRg and SI observed at baseline. High-fat feeding also elicited a 44% lower 24-h insulin level (P = 0.004) in association with a...
  • References (57)
  • Citations (58)
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References57
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#2Maria Tagliamonte (University of Naples Federico II)H-Index: 27
Last. Barbara V. HowardH-Index: 115
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Studies have shown that a high plasma non-esterified fatty acid concentration may inhibit glucose induced insulin secretion in vitro and in vivo. The effect of lowering the fatty acid concentration on the acute insulin response was investigated in first degree relatives of people with Type II diabetes in a double-blind, randomised, placebo-controlled trial. Fifty first degree relatives of people with Type II diabetes volunteered for the study. Twenty five were given acipimox (250 mg/day, four ti...
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#1Giuseppe Paolisso (University of Naples Federico II)H-Index: 77
#2B.V. HowardH-Index: 1
Over 30 years after the original description of Randle’s cycle, the mechanisms by which elevated circulating non-esterified fatty acids might be causally related to glucose intolerance in Type 2 diabetes mellitus remain uncertain. This review examines the evidence that elevated plasma NEFA can inhibit glucose-stimulated insulin secretion by pancreatic beta-cells and impair glucose- and insulin-stimulated glucose disposal by peripheral tissues. Experimental evidence beginning to examine the mecha...
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The pancreatic beta cell normally maintains a stable balance among insulin secretion, insulin production, and insulin degradation to keep optimal intracellular stores of the hormone. Elevated levels of FFA markedly enhance insulin secretion; however, the effects of FFA on insulin production and intracellular stores remain unclear. In this study, twofold elevation in total circulating FFA effected by infusion of lard oil and heparin into rats for 6 h under normoglycemic conditions resulted in a m...
232 CitationsSource
Plasma glucose and insulin responses to a graded iv infusion of glucose were compared in two groups of glucose-tolerant women divided on the basis of their insulin sensitivity. Resistance to insulin-mediated glucose disposal was measured using the insulin suppression test, and the women studied were chosen to represent the highest and lowest quartiles of insulin resistance seen in the normal population. The sensitivity of the pancreatic β-cell to glucose was assessed by measuring the glucose, in...
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To examine whether the hexosamine biosynthetic pathway might play a role in fat-induced insulin resistance, we monitored the effects of prolonged elevations in FFA availability both on skeletal muscle levels of UDP-N-acetyl-hexosamines and on peripheral glucose disposal during 7-h euglycemic-hyperinsulinemic (approximately 500 microU/ml) clamp studies. When the insulin-induced decrease in the plasma FFA levels (to approximately 0.3 mM) was prevented by infusion of a lipid emulsion in 15 consciou...
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To study the islet adaptation to reduced insulin sensitivity in normal and glucose intolerant post-menopausal women, we performed a euglycaemic, hyperinsulinaemic clamp in 108 randomly selected women, aged 58–59 years. Of the 20 women with the lowest insulin sensitivity, 11 had impaired glucose tolerance (IGT) whereas 9 had normal glucose tolerance (NGT). These women together with 15 women with medium insulin sensitivity and 16 women with high insulin sensitivity and NGT were further examined wi...
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