Proinsulin responses during oral glucose tolerance test in Korean patients with NIDDM

초록

Background : When insulin is secreted from the pancreas, a small amount of proinsulin is also secreted at the same time. Pancreatic beta cell may release immature granules richer in proinsulin contents as well as mature granules in the over-stimulated state. The significance of hyperproinsulinemia was recently reevaluated in the pathogenesis of non-insulin dependent diabetes mellitus(NIDDM). We studied proinsulin response at fasting and oral glucose tolerance test(OGTT) in NIDDM with a simple and sensitive human proinsulin radioimmunoassay system. Methods: 22 new onset non-obese NIDDM patients and 11 matched healthy controls were selected for the study. The NIDDM group was divided into 3 groups(group 1; <7.8, group 2; 7.8-11, group 3; >11.0 mmol/l) according to the fasting plasma glucose level. After an overnight fast, a 75 g OGTT was performed and samples were analyzed with proinsulin and specific human insulin radioimmunoassay kits. Results : The basal serum proinsulin level in normal control was reported as 9.29±4.19 pmol/l. The values in NIDDM group 1 and 2(18.07±9.02;p=0.04, 21.60±6.98;p=0.03) were higher than in control subjects. The molar ratio of the basal proinsulin to total insulin were also increased in NIDDM group 1 and 2(0.24, 0.28) than in control subjects(0.13, p=0.03). The basal proinsulin and proinsulin/total insulin ratio were highest in the group 2(p=0.05, than group 3). During oral glucose loading, the proinsulin response increased more slowly than total insulin response. The proinsulin and proinsulin/total insulin ratio during oral glucose loading were higher in NIDDM group 1 and group 2 than controls. Conclusion : The proinsulin responses during oral glucose loading were higher in NIDDM group 1 and 2 patients than controls. So the serum proinsulin as well as c-peptide would be used as one of the marker for impairment of secretory capacity of beta cells in NIDDM. The mechanism about the metabolic pathway of the proinsulin secretion should