Perfect Normalization of Excessive Glucagon Responses to Intravenous Arginine in Human Diabetes Mellitus With the Artificial Beta-Cell

Abstract

To elucidate the precise significance of pancreatic A-cell hypersecretion in the pathogenesis of diabetes mellitus, the change in the immunoreactive glucagon (IRG) response to intravenous arginine was studied in both nonobese, hypoinsulinemic non-insulin-dependent (NIDDM) and insulin-dependent diabetic (IDDM) subjects whose blood glucose responses and plasma immunoreactive insulin (IRI) simulated those of healthy subjects with the aid of the artificial beta-cell system that we originally developed. In both five NIDDM and five IDDM subjects, blood glucose responses and plasma IRI after arginine challenges were made equivalent to those seen in healthy subjects by infusing insulin in response to blood glucose, revealing that previously exaggerated IRG responses were made completely similar to the responses in healthy subjects. In summary, these results clearly demonstrate that the exaggerated response of A-cell secretion against arginine challenges in insulin-deficient diabetics is secondary to insulin lack, and the perfect normalization of its response is achieved only when both plasma insulin concentration and glycemic control simulate those of healthy subjects.