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Hyperproinsulinemia and insulin deficiency in the diabetic Psammomys obesus.

Abstract：

:Patients with noninsulin-dependent diabetes mellitus exhibit increased proportions of plasma proinsulin and proinsulin conversion intermediates. We used hyperinsulinemic diabetic and nondiabetic Psammomys obesus to study the possible relationship between steady state pancreatic insulin stores and the proportion of proinsulin-related peptides in the plasma and pancreas. Insulin-like peptides were separated by reverse phase HPLC and identified by pulse-chase experiments. A marked increase in the proportions of proinsulin and proinsulin conversion intermediates in the plasma and pancreas of diabetic nonfasted Psammomys was associated with 90% reduction in insulin stores of the pancreas. After a 16- to 20-h fast, the depletion of pancreatic insulin in the diabetic animals was partially corrected, and the proinsulin/insulin ratio was normalized. In contrast, nondiabetic Psammomys showed only 50% reduction in pancreatic insulin stores under nonfasting conditions, with no change in the proinsulin/insulin ratio. These findings suggest that in the diabetic Psammomys obesus, the pancreatic capacity for storage of insulin may be limited; the metabolic consequences of this limitation are amplified by increased secretory demand secondary to insulin resistance, thus facilitating the establishment of hyperglycemia, which may in itself further exacerbate pancreatic dysfunction.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Gadot M,Leibowitz G,Shafrir E,Cerasi E,Gross DJ,Kaiser N

doi

10.1210/endo.135.2.8033810

subject

Has Abstract

pub_date

1994-08-01 00:00:00

pages

610-6

issue

2

eissn

0013-7227

issn

1945-7170

journal_volume

135

pub_type

杂志文章

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