Beta Cell Response to the Hyperglycaemic Clamp in Three Patients with Insulinoma: A Study Using a Hyperglycaemic Glucose Clamp

Summary

To determine the mechanism responsible for deficient carbohydrate metabolism in patients with insulinoma, we studied three affected patients and seven normal controls using the hyperglycaemic clamp method (8.4 mmol/l) with the BIO-STATOR (GCIIS). In insulinoma patients, the amount of glucose necessary to reach the hyperglycaemic clamp was less than that required in normal controls (6.19 ∓ 1.19 mg/min/kg vs. 9.95 ∓ 0.53 mg/min/kg) (p < 0.05). There was no significant difference in metabolized glucose (M) in the stable phase of the hyperglycaemic clamp; however, the M/IRI in this phase was less in those with insulinoma (7.9 ∓ 0.50) than in controls (22.26 ∓ 4.14) (p < 0.05). There was no difference in beta cell secretory response to hyperglycaemic stimulus (defined as the increase in the concentration of C-peptide from the basal state to the stable phase of the hyperglycaemic clamp) between the two groups. Hepatic insulin extraction was significantly lower in patients with insulinoma than in normal controls (+0.72 ∓ 0.07 vs. +0.85 ∓ 0.01). Finally, the ratios of fractional turnover of glucose (K/IRI); glucose clearance/IRI and total rate of elimination of glucose from the extracellularpool/IRI were also all lower in patients with insulinoma than in controls (p < 0.05). These data support the conclusion that deficient glucose metabolism seen in these patients is not related to a lack of response to glucose on the part of normal or neoplastic islet tissue. The lesser quantity of infused glucose needed to reach the clamp in patients with insulinoma; the reduced ratio of glucose disappearance to immunoreactive insulin; and the reduced rate of glucose metabolism with respect to immunoreactive insulin levels, all suggest the existence of “insufficient hormonal activity”, probably related to hypersecretion of proinsulin or proinsulin fragments displaying cross-reactivity with insulin, but with lesser biological activity. A further possibility is the decrease of the insulin's receptor number by the patients' hyperinsulinemia.

Key-Words

Insulinoma - Hyperglycaemic Clamp-Beta Cell - Hepatic Insulin Extraction - Glucose Metabolism