Hyperproinsulinaemia and islet dysfunction in the NIDDM-like syndrome of Psammomys obesus.

Abstract

Patients with Type 2, non-insulin dependent diabetes (NIDDM) exhibit elevated plasma proinsulin to insulin ratios [1–9]. Recently, it has been shown that the plasma proinsulin-like fraction in these patients as well as in normal individuals is comprised of both proinsulin and partially cleaved proinsulin, primarily des 31, 32 proinsulin [7,8]. It is assumed that the elevated ratio between proinsulin-related peptides and insulin reflects a β-cell abnormality, since the metabolic clearance rate of these peptides does not differ appreciably between normal individuals and patients with diabetes [10]. Reduction of the plasma glucose concentration in patients with NIDDM, irrespective of the means, was shown to improve insulin production and reduce the degree of hyperproinsulinaemia [3, 11–15]. These observations in man, as well as studies in animal models of diabetes [16–23] have led to the notion that hyperglycaemia per se might be implicated in the generation of a defective β-cell secretory response [24]. Alternatively, hyperglycaemia may play an important contributory role by amplifying a genetically determined β-cell defect, which may not be apparent until unmasked by a chronic increase in secretory demand.