Effect of hyperkalemia on insulin secretion

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 less than 0.05). We concluded that only marked increases in plasma potassium concentration stimulate pancreatic insulin secretion.     

Ethanol influence on insulin secretion from isolated rat islets

Summary This study was done to delineate the role of - and -adrenergic receptors and cyclic AMP in the mechanism of ethanol effects on insulin release from isolated islets. Rats were given an -adrenergic blocker, phentolamine, or a -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.Supported by the U.S. Veterans Administration     

Effect of vincristine on glucose-induced insulin secretion in man

Summary 60 min after the injection of therapeutic doses of vincristine for cancer chemotherapy, there is a reduction of the total (40%) and of the acute phase (43%) areas of insulin secretion induced by a 5-g i.v. glucose load, and the constant of glucose utilization is reduced by 25%. No differences are observed after 3 5-g i.v. glucose loads given at hourly intervals in control subjects.Acknowledgment. The authors are grateful to Mr S. Castiglioni and to Miss Maria Luisa Fuser for their skillful technical assistance.     

Effect of dihydroergocristine infusion on tolbutamide-induced insulin secretion in man

Summary The insulinemic response to 1 g of tolbutamide i.v. is greatly enhanced (+145%) after a 60-min infusion of the -lytic dihydrogenated ergot alkaloid, dihydroergocristine (83.3 m/min, corresponding to a total dose of 5 mg) in 7 healthy subjects. No differences are observed in the glycemic responses.Acknowledgment. The authors are grateful to Mr Franco Della Sala, M.D., for his skillful technical assistance.     

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     

Effect of dihydroergocristine infusion on tolbutamide-induced insulin secretion in man.

The insulinemic response to 1 g of tolbutamide i.v. is greatly enhanced (+ 145%) after a 60-min infusion of the alpha-lytic dihydrogenated ergot alkaloid, dihydroergocristine (83.3 micrograms/min, corresponding to a total dose of 5 mg) in 7 healthy subjects. No differences are observed in the glycemic responses.     

Hepatic glucose signals vagally modulate the cyclicity of gastric motility in rats

The cyclicity and intensity of gastric motlity were examined following glucose injection into the portal vein with an intragastric balloon in anesthetized rats. Enhanced gastric motility caused by insulin administration was influenced by 4 mM glucose (25 l) injected into the portal vein; glucose provoked a shift in the cyclicity power spectrum without any change in intensity. The peak power spectrum shifted from 4.0–5.0 cpm to 2.0–3.0 cpm. Hepatic branch vagotomy abolished the response.The results suggest that glucose signals in the hepatic vagal branch modulate the cyclicity of gastric motiligy.     

Smooth muscle in the hepatic artery,portal vein and hepatic vein within the liver of the raccoon and guinea pig

Summary The amount and arrangement of smooth muscle in the intrahepatic vessels suggests that the guinea pig would be a good animal model for studying mechanisms controlling intrahepatic portal vein blood flow, while the raccoon would be good for studying hepatic vein mechanisms of control.     

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.     

Reversal of net secretion to net absorption of potassium in rat large intestine by dietary potassium depletion

Summary Feeding rats a diet low in potassium and high in sodium for 2 weeks led to a reversal of net potassium secretion to net potassium absorption in ligated segments of distal large intestine (colon descendens and rectum) under in-vivo conditions. This change in the direction of net potassium transport is probably important for the maintenance of potassium homeostasis.The technical assistance of Mrs U. Seeliger is gratefully acknowledged.     

Effects of intraventricular administration of insulin on thyrotropin secretion in rats

Intraventricular administration of insulin stimulates increases in the levels of thyrotropin-releasing hormone and thyrotropin in rats.     

Effects of intraventricular administration of insulin on thyrotropin secretion in rats

Summary Intraventricular administration of insulin stimulates increases in the levels of thyrotropin-releasing hormone and thyrotropin in rats.Ovine insulin was kindly supplied from Shimizu Pharm. Co., Ltd. (Japan).Rat TSH radioimmunoassay kit was kindly supplied by NIAMDD.     

Some thoughts on the importance of insulin in the regulation of the blood glucose level

Insulin can influence rates of glucose utilization by muscle and possibly other tissues via both direct and indirect effects. It can control the rate of fatty acid mobilization from adipose tissue and the rate of fatty acid oxidation in muscle, and the latter inhibits glucose utilization and oxidation. Insulin may influence the levels of insulin-like growth factors I and II, both of which have effects on rates of glucose utilization by muscle. The intertissue cycle between glucose and lactate — the Cori cycle, which is influenced by insulin — may provide another novel mechanism for control of blood glucose. How far other anti-insulin hormones affect these processes is not clear.     

Insulin secretion: The effector system

Conclusions Studies of the role of the microtubule-microfilamentous system in insulin secretion have been widened by continuing experimentation and analysis to provide a comprehensive working hypothesis which embraces ideas of the way in which the polymerization of microtubules and microfilaments may be regulated and how these cytoskeletal components may act together to enhance the process of granule movement. It is also possible to speculate about, but not yet to demonstrate, the way in which the activities of this effector system could be regulated by calcium and by cyclic AMP, which are essentially involved in the regulation of rates of secretion.