Early changes in beta-cell function and insulin pulsatility as predictors for type 2 diabetes.
Peripheral insulin concentrations oscillate because of insulin secretory bursts every 6-10 min, which are the main source of overall insulin release. Regulation of insulin secretion occurs by modification of the mass and to some extent the frequency of the individual insulin secretory bursts. This oscillatory pattern, which is important for insulin action, is observed at the level of the individual beta-cells and in the islets, both in vitro (in the isolated perfused pancreas) and in vivo. It has therefore been suggested that beta-cells act as pacemakers and that co-ordination among islets is achieved by a neuronal network within the pancreas. Type 2 diabetes mellitus is characterised both by impaired release of insulin and by resistance to the action of insulin. Routine screening procedures for insulin secretion yield little predictive value for later development of diabetes but more sophisticated methods using time-series analysis of diurnal, ultradian and rapid oscillatory insulin secretion reveal the presence of profound defects in glucose-intolerant individuals. Furthermore, studies of rapid pulsatile insulin secretion have revealed defects in glucose-tolerant first-degree relatives of patients with Type 2 diabetes. Application of repeated minimal glucose infusions has further improved the discrimination between insulin release in health and diabetes, suggesting that this method may be suitable for smaller prospective studies of the development of diabetes. Repaglinide, a novel prandial glucose regulator, improves the insulin secretory burst mass in healthy people.
Pørksen
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Medical Department M (Endocrinology and Metabolism), Arhus University Hospital, Arhus, Denmark. porksen@dadlnet.dk
D002219:Carbamates / Q000627:therapeutic use; D002940:Circadian Rhythm; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000502:physiology*; D010179:Pancreas / Q000378:metabolism; D010880:Piperidines / Q000627:therapeutic use; D011237:Predictive Value of Tests; D011673:Pulsatile Flow
D002219:Carbamates; D007004:Hypoglycemic Agents; D007328:Insulin; D010880:Piperidines; C072379:repaglinide