A characteristic feature of non-insulin-dependent diabetes mellitus (NIDDM) is the lack of an acute insulin response to intravenous glucose with maintenance of the response to other secretagogues. It has been hypothesized that impaired glucose sensing stems from defective β-cell glucokinase. It remains unclear whether decreased pancreatic glucokinase activity will produce defects of insulin secretion similar to those observed in NIDDM. In this study, the effects of glucosamine on glucokinase activity and on islet function were assessed in vitro and in vivo. Glucosamine (5 mmol/l) reduced glucokinase activity in islet homogenate and diminished the insulin response to glucose (200 mg/dl) by isolated islets, whereas the response to arginine (20 mmol/l at 100 mg/dl glucose) was unaffected. In conscious normal rats, glucosamine lowered plasma insulin, followed by an increase in blood glucose. Administration of glucosamine 10 min before an infusion of glucose (10 mg · min−1 · 15 min) reduced the insulin response. The primary effect was an attenuation of the first-phase insulin response relative to the decreased basal insulin levels. Arginine (10 mg · min−1 · 15 min) induced biphasic insulin release in both groups. Although glucosamine slightly reduced the absolute insulin response, it was normal relative to preinfusion levels. In all experiments, glucagon secretion was unaffected by glucosamine. The results indicate that glucosamine inhibits β-cell glucokinase activity in vitro. In addition, glucosamine impairs glucose- but not arginine-induced insulin secretion. We conclude that glucosamine, probably via a reduction of glucokinase activity, impairs insulin secretion in a manner comparable to that seen in NIDDM.
Glucosamine Inhibits Glucokinase In Vitro and Produces a Glucose-Specific Impairment of In Vivo Insulin Secretion in Rats
NIDDM, non-insulin-dependent diabetes mellitus; MODY, maturity-onset diabetes of the young; MEM G100, minimal essential medium containing 100 mg/dl glucose; RIA, radioimmunoassay; AUC, area under the curve; IRI, immunoreactive insulin; AUCgluc, area under the glucose curve; IRG, immunoreactive glucagon; AUCIRI, area under the curve for immunoreactive insulin; AUC%IRI, area under the percentage change curve for immunoreactive insulin; Kg, glucose disposal rate.
Börk Balkan, Beth E Dunning; Glucosamine Inhibits Glucokinase In Vitro and Produces a Glucose-Specific Impairment of In Vivo Insulin Secretion in Rats. Diabetes 1 October 1994; 43 (10): 1173–1179. https://doi.org/10.2337/diab.43.10.1173
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