M Lorenzetti

The biguanide compound metformin prevents desensitization of human pancreatic islets induced by high glucose

Pancreatic islet desensitization by high glucose concentrations is a temporary and reversible state of beta-cell refractoriness to glucose (and possibly other secretagogues), due to repeated or prolonged pre-exposure to increased glucose concentrations. We evaluated whether the oral antidiabetic agent metformin affects this phenomenon in isolated, human pancreatic islets, and whether the possible effects of the biguanide are influenced by the presence of a sulphonylurea, glyburide. Islets prepared from five human pancreases were incubated for 24 h in M199 culture medium containing either 5.5 or 22.2 mmol/l glucose, with or without a therapeutic concentration (2.4 microg/ml) of metformin. Then, the islets were challenged with either 3.3 mmol/l glucose, 16.7 mmol/l glucose, or 3.3 mmol/l glucose + 10 mmol/l arginine, and insulin release was measured. After incubation in the absence of metformin, the human islets exposed to 22.2 mmol/l glucose showed no significant increase in insulin release when challenged with 16.7 mmol/l glucose (confirming that hyperglycemia desensitizes pancreatic beta-cells). In the presence of metformin, the islets fully maintained the ability to significantly increase their insulin release in response to glucose, even when previously exposed to 22.2 mmol/l glucose. No major effect on arginine-induced insulin release was observed, whatever the culture conditions. The protective action of metformin was observed also when glyburide was present in the incubation medium, whereas the sulphonylurea alone did not affect insulin release from the islets previously exposed to high glucose concentrations. These in vitro results suggest that metformin can prevent the desensitization of human pancreatic islets induced by prolonged exposure to increased glucose concentrations.

Effects of glibenclamide and metformin (alone or in combination) on insulin release from isolated human pancreatic islets

Abstract Isolated human pancreatic islets were prepared by collagenase digestion and density gradient purification, and the effects of glibenclamide (0.5 and 5.0 µmol/l) and metformin (20 and 200 µmol/l), alone or in combination, on insulin release were evaluated at varying glucose concentrations. At 3.3 mmol/l glucose level, the addition of 5.0 µmol/l glibenclamide or 5.0 µmol/l glibenclamide plus 200 µmol/l metformin caused a significant increase of insulin release, compared with glucose alone. At 16.7 mmol/l glucose concentration, a significant increase of insulin secretion, compared with glucose alone, was produced by the addition of either 5.0 µmol/l glibenclamide, 200 µmol/l metformin, or both 5.0 µmol/l glibenclamide and 200 µmol/l metformin. The effect of the combination of the two drugs was significantly higher than that with either drug used alone. Thus, glibenclamide was shown to have an insulinotropic effect on human islets at both low and high glucose concentrations, and metformin at high glucose concentrations. A possible synergistic effect of glibenclamide and metformin at high glucose concentrations is also suggested.

Long-term survival and function of isolated bovine pancreatic islets maintained in different culture media

Bovine islets are being evaluated for their potential in transplantation studies. We studied the recovery, morphology, and function of purified bovine islets cultured up to 4 weeks under varying conditions. Approximately 60% of the initial islet mass could be recovered after 4 weeks at 37°C in CMRL 1066 or M 199 culture medium, and the cultured islets were well preserved histologically and viable both in vitro and in vivo. On the other hand, culture with RPMI 1640 caused disaggregation of the islets within a few days, with altered in vitro viability. Thus, culturing purified bovine islets with appropriate media is a suitable procedure to maintain islet mass, morphology, and function in the long term.

Deterioration of renal function in a nephropathic diabetic patient during omeprazole plus amoxicillin therapy forHelicobacter pylori-associated duodenal ulcer

Helicobacter pylori may be the cause of a variety of gastrointestinal tract diseases [1]. When H. pylori is found in association with gastric or duodenal ulcer, combined treatment with omeprazole and amoxicillin is a simple and effective therapy [l, 2]. Both drugs are considered to have very few side-effects [1] and are therefore widely employed in clinical practice. In the present report, we deal with a diabetic patient who showed deterioration of renal function upon treatment with omeprazole and amoxicillin for H. pylori-associated duodenal ulcer.