Abstract

Beta‐cell function is impaired in type 2 diabetes. Identifying related plasma metabolites related to insulin secretion may help identify novel treatment targets. Intravenous glucose‐stimulated insulin secretion (GSIS) was measured in healthy subjects before and after acute 24‐hour experimental‐elevation of plasma glucose (+5 mM). GSIS was also measured in age/BMI‐matched type 2 diabetic (T2D) patients. The plasma metabolite profile (358 compounds) was determined using LC/GC‐MS and correlated with group differences in GSIS and with hyperglycemia‐induced changes in GSIS. GSIS was lower in T2D compared to controls (6.8±0.8 vs. 10.1±0.9 pmol/kg/min; P<0.05), but elevated following experimental hyperglycemia in healthy controls (13.1±0.8). Hexadecanedioate, octadecanedioate and 3‐aminoisobutyrate were significantly correlated with GSIS (r= −0.66,−0.61,−0.56; P<0.05) showing the same direction of change in both acute and chronic models of hyperglycemia. These plasma metabolites are biomarkers of beta‐cell function in humans and may reveal novel therapeutic targets. The effect of these compounds on GSIS in perifused pancreatic islets is currently being determined.

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