Decreased insulin secretory capacity and normal pancreatic B‐cell glucose sensitivity in non‐obese patients with NIDDM

We investigated the dose‐response characteristics of glucose‐induced insulin release and the influence of hyperglycaemia on arginine‐induced insulin secretion in eight non‐obese subjects with NIDDM and in eight non‐diabetic volunteers. Plasma C‐peptide levels, achieved during 60 min hyperglycaemic clamps with and without the infusion of a primed continuous infusion of arginine (infusion rate 15 mg kg‐1 min‐1) during the last 30 min, were analysed with a modified Michaelis‐Menten equation. The insulin secretory capacity (Vmax) for glucose‐stimulated insulin release snowed a trend towards a negative correlation with the fasting blood glucose in the NIDDM subjects (r=0.68, P=0.6); it was lower than the Vmax of non‐diabetic controls (2.2±0.2 vs 4.2±0.4 nmol 1‐1 respectively; P<0.001). The ED50 (half maximal stimulating blood glucose concentration) of the second‐phase glucose‐stimulated insulin release (determined from the plasma C‐peptide levels at 60 min) was not significantly different from the ED50 of the controls (11.9±0.8 vs 13.3±1.9 mmol 1‐1 respectively; P>0.2). Combined glucose‐arginine stimulation significantly increased insulin release. The Vmax for both phases were significantly lower in NIDDM patients than in controls (2.3±0.2 vs 5.0±0.9 and 3.8±0.5 vs 8.5±0.9 nmol 1‐1 respectively; P<0.01). In both NIDDM patients and controls, the ED50 of the influence of glucose on first‐phase arginine‐induced insulin release was significantly lower than the ED50 for the second phase (8.2±0.8 vs 10.5±1.1 mmol 1‐1 (NIDDM) and 9.4±1.4 vs 11.6±0.9 mmol 1‐1 (non‐diabetic subjects) respectively; P<0.02). No differences in ED50 were seen between the two groups. In NIDDM patients, the fasting blood glucose level was negatively correlated with the Vmax of the second phase of glucose‐arginine‐induced insulin release (r=‐0.70, P=0.05). We conclude that (1) insulin secretory capacity is reduced in NIDDM both for stimulation with glucose and with arginine; (2) the B‐cell glucose sensitivity is normal in patients with NIDDM.