Serum Proinsulin Responses during Oral Glucose Tolerance Test in patients with Non-insulin Dependent Diabetes Mellitus

Nam, Moon Suk; Hong, Seong Bin; Kim, Yeo Joo; Kim, Mi Rim; Kim, Yong Seong; Hyun, In Young; Kwak, In Ho

Abstract

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-stirnulated 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 was reported as 9.29+/-4.19 pmol/L in normal control and as 18.09+/-9.32 pmol/L(p=0.04, compared with control) in diabetic group. The values in NIDDM group 1 and 2(18.07+/-9.D2; p=0.04, 21.60+/-6.98; p=0.03) were higher than in control. The molar ratia of the basal proinsulin to total insulin were also increased in NIDDM group 1 and 2(0.24, 0.28) than in control subjmts(0.13, p=0.03). The basal proinsulin and proineulin/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 cantrols.
CONCLUSION
The basal proinsulin level in diabetic group was higher than in normal control. The proinsulin responses during oral glucose loading were higher in diabetic group 1 and 2 than controls. The proinlulin response increased more slowly than total insulin response during oral glucose loading. So we conclude that the proinsulin secretion frorn pancreatic beta cell is impaired in diabetic group. The mechanism about the metabolic pathway of the proinsulin secretion should be studied more.