Ethanol influence on insulin secretion from isolated rat islets

This study was done to delineate the role of alpha- and beta-adrenergic receptors and cyclic AMP in the mechanism of ethanol effects on insulin release from isolated islets. Rats were given an alpha-adrenergic blocker, phentolamine, or a beta-adrenergic blocker, propranolol. In addition, ethanol 1 g/kg was given intragastrically 1 h prior to sacrifice. Glucose mediated insulin release from isolated islets was enhanced by phentolamine and decreased by propranolol. Ethanol treatment inhibited glucose-induced insulin release from isolated islets of control rats as well as those given phentolamine and/or propranolol. Insulin release from isolated islets in response to dibutyryl-cyclic AMP was attenuated by ethanol. Theophylline enhanced glucose mediated insulin release from control islets but ethanol treatment produced a significant inhibition of insulin response. The data suggest that the site of action of the deleterious effects of ethanol on insulin release from isolated islets in rat does not involve adrenergic system and cyclic AMP.     

Dysfunctional insulin secretion in type 2 diabetes: role of metabolic abnormalities

Insulin secretion is finely tuned to the requirements of tissues by tight coupling to prevailing blood glucose levels. The normal regulation of insulin secretion is coupled to glucose metabolism in the pancreatic B cell, a major but not exclusive signal for secretion being closure of K⁺ATP (adenosine triphosphate)-dependent channels in the cell membrane through an increase in cytosolic ATP/adenosine diphosphate. Insulin secretion in type 2 diabetes is abnormal in several respects due to genetic causes but also due to the metabolic environment of the pancreatic B cells. This environment may be particularly important for the deterioration of insulin secretion which occurs with increasing duration of diabetes. Factors in the environment with potential importance include overstimulation, a negative effect of hyperglycemia per se (‘glucotoxicity’) as well as adverse effects of elevated fatty acids (‘lipotoxicity’). Elucidating the mechanisms behind these factors as well as their clinical importance will pave the way for treatment which could preserve B-cell function in type 2 diabetic patients. Received 4 October 1999; received after revision 1 November 1999; accepted 3 December 1999     

Lack of influence of vitamin D deficiency on insulin release from the isolated pancreatic islets of rats

Pancreatic islets were isolated from young (100 g) and adult (390 g), normal and vitamin D deficient male Sprague-Dawley rats. The release of insulin from leucine-stimulated or glucose-stimulated islet was not altered by vitamin D deficiency. The in vitro addition of either 25-hydroxy- or 1,25-dihydroxyvitamin-D had no effect on insulin release from either normal or vitamin D deficient islets. We conclude that the earlier report (Normal et al., Science 209 (1980) 823-825) on vitamin D deficiency depressing insulin secretion from the perfused pancreas must be related to the vitamin's effect on insulin synthesis and not the islet's release of insulin.     

Effect of hyperkalemia on insulin secretion

Summary The effect of hyperkalemia on insulin secretion remains undefined. We evaluated portal and peripheral insulin levels in anesthetized dogs after infusions of KCl. The mean maximal increase in peripheral plasma potassium at infusion rates of 0.2 mEq/kg/h was 0.68±0.20 mEq/l. There were no significant increases in either portal or peripheral insulin levels. In contrast, in six dogs whose plasma potassium concentration increased in each case by more than 2.0 mEq/l (infusion rate of 0.5 mEq/kg/h), portal insulin levels increased fivefold (p<0.05). We conclude that only marked increases in plasma potassium concentration stimulate pancreatic insulin secretion.     

Effects of pregnancy on the glucose-induced insulin release from cultivated pancreatic islets of the rat

Summary 7-day-cultured islets from pregnant Wistar rats released at 5.6 mM glucose significantly more insulin than islets from nonpregnant rats, whereas in vivo this heigthened glucose sensitivity is lost 48 h post partum.Investigations carried out as a part of the Forschungsprojekt Diabetes mellitus und Fettstoffwechselstörungen supported by the Ministry of Health of German Democratic Republic.     

Kinetics of insulin secretion in response to glucose by isolated islands of Langerhans from the fetal rat]

Isolated islets of Langerhans from 21.5 day-old foetal Rats were studied in a perifusion system in vitro. The overall dynamics of insulin release by the foetal islets in response to glucose 13.9 mM is biphasic and qualitatively similar to that obtained with islets of adult Rats. The magnitude of the initial phase of insulin secretion is similar for the foetal and adult islets. The second phase is fourfold higher in the adult than in the foetus. The response of foetal islets occurs, 45 to 60 sec. after the increase of glucose concentration in the medium and a maximum insulin release for the first phase is obtained with a lag period of 2 min. The difference between foetal and adult islets is essentially quantitative.     

Effects of pregnancy on the glucose-induced insulin release from cultivated pancreatic islets of the rat.

7-day-cultured islets from pregnant Wistar rats released at 5.6 mM glucose significantly more insulin than islets from nonpregnant rats, whereas in vivo this heigthened glucose sensitivity is lost 48 h post partum.     

Rapid effects of insulin on cyclic GMP location in an intact protozoan

We studied rapid changes in location of cyclic GMP inTetrahymena pyriformis. Insulin caused cGMP localization in cilia and near the plasma membrane (0.5–1 min). Later (1–5 min) cGMP localization was diffuse in cytoplasm with perinuclear accentuation. Inactive insulin analogs did not elicit these changes.     

The influence of diuretics on the absorption of salts,glucose, and water from the isolated small intestine of the rat

Zusammenfassung (1) Unter dem Einfluss von Mersalyl (5×10^–4 m) und Hydrochlorothiazid (2×10^–3 m) nimmt die Cl-Konzentration in der resorbierten Flüssigkeit ab, während die Na-Konzentration gleich bleibt und die Glucose-Konzentration ansteigt. Gleichzeitig kommt es zu einer osmotisch äquivalenten Einschränkung der Wasserresorption.(2) Die prozentuale Hemmung der Wasserresorption durch Mersalyl nimmt zu bei höherer Cl^–-Konzentration in der angebotenen Flüssigkeit und hängt zwischen pH 6,5 und 7,4 nicht von der H⁺-Konzentration ab.(3) Die Wirkung von Mersalyl lässt sich mit Cystein aufheben und ist auchin vivo an der abgebundenen Darmschlinge nachweisbar.(4) Der Glucosetransport und die Calciumresorption werden durch Mersalylkonzentrationen, die die Wasser-und Natriumresorption um 30% hemmen, nicht beeinträchtigt. Der Durchtritt von Calcium durch die Darmwand ist auf das 1,5fache erhöht, es häuft sich dabei in der resorbierten Flüssigkeit an.(5)p-Chloromercuribenzoat hemmt in Konzentrationen, die die Natrium- und Wasserresorption um 40% vermindern, den Glucosetransport ebenfalls um 40%. Im Unterschied zu Mersalyl setzt es die Cl^–-Konzentration der resorbierten Flüssigkeit nicht herab.

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A preliminary report was presented at the 25th Meeting of the German Pharmacological Society in September 1959, Basel.