The effect of karela (Momordica charantia), a fruit indigenous to South America and Asia, on glucose and insulin concentrations was studied in nine non-insulindependent diabetics and six non-diabetic laboratory rats. A water-soluble extract of the fruits significantly reduced blood glucose concentrations during a 50 g oral glucose tolerance test in the diabetics and after force-feeding in the rats. Fried karela fruits consumed as a daily supplement to the diet produced a small but significant improvement in glucose tolerance. Improvement in glucose tolerance was not associated with an increase in serum insulin responses.These results show that karela improves glucose tolerance in diabetes. Doctors supervising Asian diabetics should be aware of the fruit's hypoglycaemic properties.

The effect of melatonin (100 µg/ml) on basal and glucose-induced insulin secretion was investigated using micro-dissected pancreatic islets of obese hyper-glycaemic mice and their normal lean littermates, and pieces of rat pancreas. Melatonin had no significant effect on basal insulin secretion from both normal and obese mouse islets, but significantly reduced basal insulin secretion from pieces of rat pancreas. However, glucose-induced insulin secretion was significantly inhibited by melatonin in both preparations. A constant infusion of melatonin into rats undergoing intravenous glucose tolerance tests did not alter blood sugar levels and produced only a marginal decrease in plasma insulin levels. It is suggested that melatonin may be involved in the monoaminergic regulation of insulin secretion.

Effect of metformin on insulin receptor binding and glycaemic control in type II diabetesTo investigate the effect of metformin on insulin receptor binding and diabetic control, eight obese type II diabetic patients were studied before treatment, after one and four weeks of taking metformin (500 mg thrice daily), and four weeks after withdrawal of the drug. After one and four weeks of treatment the number of erythrocyte insulin receptors had increased by 116% and 184% respectively. This was due almost entirely to an increase in the number of low affinity binding sites. The number of receptors was still raised four weeks after metformin had been withdrawn. Diabetic control as assessed by urinary glucose, glycosylated haemoglobin (HbA5), and glucose tolerance values was significantly improved during metformin treatment, while plasma insulin concentrations were not altered. These results indicate that metformin produces a rapid and protracted increase in low affinity insulin receptors in type II diabetes, associated with greater insulin sensitivity and improved diabetic control.

The effect of metformin on hepatocyte insulin receptor binding was examined in normal, streptozotocin diabetic and genetically obese diabetic (ob/ob) mice. In normal mice, chronic administration of metformin (60 mg X kg-1 X day-1 for 50 weeks) increased the number of low affinity receptors by 148%. During acute studies, metformin increased (30%) the number of low affinity receptors after 24 h. When metformin was withdrawn after treatment for 96 h, the number of low affinity receptors decreased, approaching control values by 48 h. In severely insulin resistant ob/ob mice, the concentrations of high and low affinity receptors were reduced by 60% and 27%, respectively. A high dose of metformin (240 mg X kg-1 X day-1 for 4 weeks) increased the concentration of high and low affinity receptors in ob/ob mice by 63% and 86%, respectively. However, the hypoglycaemic response to exogenous insulin was not altered. In streptozotocin-diabetic mice, the number of low affinity receptors was increased by 68% compared with normal mice. Metformin (60 mg X kg-1 X day-1 for 10 weeks) did not significantly alter the number of insulin receptors in streptozotocin-diabetic mice, but the hypoglycaemic response to exogenous insulin was improved by 94%. The results raise the possibility that metformin might affect post-receptor sites of insulin action independently of effects at the receptor level.

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