Responses of plasma insulin C-peptide and proinsulin-like components to glucose and glucagon in the pig.

This study was undertaken to evaluate the relative contribution of insulin, proinsulin-like components (PLC) and C-peptide toward plasma levels of immuno reactive insulin (IRI) and C-peptide immunoreactivity (CPR) in the pig and to elucidate the mode of secretion of PLC in the early phase of insulin release. Following the intravenous glucose loads, the concomitant secretion of CPR with that of IRI occured rapidly and the maximum plasma level of IRI was observed at an earlier time than that of CPR. Following the intravenous glucagon injection, the maximum plasma levels of IRI and CPR were observed at the same time in the early phase. After the gel filtration of acid alcohol extracts of plasma in a fasted state, a very small amount of PLC and a small amount of C-peptide as well as a small amount of insulin were detected. The results obtained from the gel filtration of extracts revealed that the increased amounts in IRI and CPR after the injection of glucose or glucagon consisted mostly and respectively of insulin and C-peptide in the pig, because the concentration of PLC increased only slightly in the early phase. In fact, plasma levels of CPR and IRI were essentially and respectively paralleled to those of insulin and C-peptide which were assayed after the gel filtration of extracts. In addition, the slight elevation of PLC in the early phase after these stimulations indicated that PLC was elicited into blood circulation at the same time of the secretion of insulin and C-peptide.     

Glucose turnover and metabolic and hormonal changes in ethanol-induced hypoglycaemia.

Infusion of 67 g ethanol over four hours in fasted, non-obese normal men (a) induced hypoglycaemia by inhibiting gluconeogenesis; (b) produced noticeable increases in blood lactate, 3-hydroxybutyrate, and free fatty acid concentrations; (c) depressed plasma growth hormone concentrations, despite hypoglycaemia; and (d) raised plasma cortisol concentrations before significant hypoglycaemia occurred. These metabolic changes were explained by the reduction of redox state which accompanies ethanol oxidation. The pronounced changes in metabolic values recorded during this study suggested that the use of parenteral feeding regimens including ethanol needs to be reconsidered.     

Glucose, immunoreactive insulin and C-peptide immunoreactivity in patients with acute viral hepatitis

Carbohydrate intolerance with high insulin levels are a consistent finding in acute and chronic liver diseases. It has been recently clarified that in cirrhotic patients hyperinsulinism is related to decreased hepatic clearance, but the role of liver cell damage or portal systemic shuntings is still unclear. Therefore, we assessed glucose, immunoreactive insulin (IRI) and C-peptide immunoreactivity (CPR), in the basal state and after oral and intravenous glucose load, in fifteen patients with acute viral hepatitis (AVH), a liver disease where cell necrosis is prominent. CPR is a useful tool for investigation of hyperinsulinism as, according to previous reports, it is not - or is only to a limited degree - metabolised by the liver. Our results confirm the carbohydrate intolerance, with high IRI levels, in the early stage of AVH. CPR levels were significantly increased before and after glucose load. This study suggests that liver cell damage plays a key role in the pathogenesis of hyperinsulinism in liver diseases and high CPR values seem also to be related to liver damage.     

Effect of isoproterenol on the plasma C-peptide and insulin levels in humans

There are conflicting reports on the effect of stimulation of the beta-adrenergic receptors on insulin removal by the liver. It was, therefore, the aim of the present study to clarify that problem. Four experiments have been carried out on a group of 8 healthy female volunteers: (1) isoproterenol was infused intravenously, (2) glucose was infused intravenously, (3) isoproterenol was infused with glucose, and (4) infusion of isoproterenol and glucose was preceded by administration of propranolol (the beta-adrenergic blocking agent). The concentration of C-peptide and insulin was determined in plasma from the antecubital vein. It has been found that stimulation of the beta-adrenergic receptors with isoproterenol reduces insulin removal by the human liver. This effect of isoproterenol is prevented by blockade of the beta-adrenergic receptors with propranolol.     

Effect of acute ethanol load on plasma immunoreactive insulin and glucagon.

The effect of a single large dose of ethanol (5 mg/kg body weight) on plasma glucagon (IRG) and insulin (IRI) concentrations was studied in rats fasting for 24 hr. Hepatic cAMP concentration and blood glucose were also estimated and correlated with hormonal changes. Plasma IRG concentrations had doubled by the first sampling time (2 hr) and remained at this level up to 16 hr after ethanol administration. Plasma IRI concentrations were not affected by ethanol. Hepatic cAMP concentrations reflected changes in the plasma insulin/glucagon ratio, which seems to be the major determining factor for hepatic cAMP even during ethanol oxidation. Hypoglycemia was not found in the ethanol group during the experimental period of 24 hr, and it was therefore concluded that ethanol may stimulate glucagon secretion in rats even without concurrent hypoglycemia. Possible mechanisms for the action of ethanol on the endocrine pancrease are discussed.     

Plasma glucagon, insulin and glucose responses to intravenous arginine infusion in the rat

Plasma glucagon (IRG), insulin and glucose responses to intravenous arginine infusion in the rat were studied. Three doses of arginine hydrochloride were infused into fasted rats: 0.2 gm/kg b.w., 0.5 gm/kg b.w., and 1 gm/kg b.w. The 0.2 gm/kg dose did not result in significant elevation of plasma IRG or insulin. Both the 0.5 and 1 gm/kg doses produced a significant increase in glucagon and insulin levels within 5 minutes of starting the infusion. The 1 gm/kg dose was most effective in stimulating secretion of both hormones. This dose produced a 250% rise in the plasma IRG compared to 80% peak rise with the 0.5 gm/kg dose (p less than .01) and 1055% rise in insulin levels compared to a peak level of 225% above baseline with the 0.5 gm/kg dose (p less than .001). These results demonstrate the effectiveness of intravenous arginine in the stimulation of glucagon and insulin secretion in the rat.     

Plasma insulin and glucagon and their release from pancreatic islet in hyperosmolar diabetic rat.

In order to investigate the metabolic abnormalities in hyperosmolar diabetes from the viewpoint of insulin or glucagon, experimental hyperosmolar diabetes was produced by a combination of cortisol injection and water deprivation or only by the latter in streptozotocin-induced moderately hyperglycemic rat. They had a high blood glucose level and high plasma osmotic pressure. Fasting plasma insulin tended to decrease in the dehydrated state whether diabetic or not. Fasting plasma glucagon was increased to 0.047 +/- 0.009 nmol/l (P less than 0.05) in the non-diabetic dehydrated state (normal 0.026 +/- 0.004 nmol/l), and a similar high level of plasma glucagon was observed in the dehydrated diabetic rat (0.052 +/- 0.020 nmol/l), especially after cortisol treatment. In isolated rat islet, insulin released from the dehydrated diabetic rat at a high concentration of glucose was to some extent lower than that of diabetic rat, and released IRG vice versa. The insulin:glucagon ratio in the presence of high glucose was significantly lower in the dehydrated diabetic rat than in the normal rat (P less than 0.01). In the diabetic rat this ratio was not significantly different. This finding was also consistent with the results of in vivo experiments. Thus more catabolic hormonal changes were found in in vivo and in vitro studies in the hyperosmolar diabetic rat.     

Effect of pinealectomy on plasma glucose, insulin and glucagon levels in the rat

In an attempt to know the role of the pineal gland on glucose homeostasis, the blood plasma concentrations of glucose, insulin and glucagon under basal conditions or after the administration of nutrients were studied in the jugular vein of conscious pinealectomized (Pn), melatonin-treated pinealectomized (Pn + Mel) and control (C) rats. Glucose levels were smaller in C than in Pn rats, while immunoreactive insulin (IRI) concentrations were significantly greater in C than in Pn rats. Contrary to this, immunoreactive glucagon (IRG) levels were significantly greater in Pn than in C animals. Melatonin treatment of Pn rats induces an increase of IRI concentrations and a reduction in IRG levels. Similar changes were obtained when hormonal determinations were carried out in portal blood plasma. Although ether anesthesia increases circulating glucagon levels in the porta and cava veins, the qualitative changes of plasma insulin and glucagon in Pn and Pn + Mel were similar to those found in conscious rats. To determine the effects of nutrients on pancreatic hormone release, intravenous arginine or oral glucose were administered to the animals of the three experimental groups. In C rats, both glucose and IRI levels reached a peak 30 minutes after glucose ingestion, decreasing thereafter. However, in Pn rats a glucose intolerance was observed, with maximum glucose and insulin concentrations at 60 minutes, while in Pn + Mel animals, glucose and IRI concentrations were in between the data obtained with the other two groups. Furthermore, glucose ingestion induced a significant reduction of IRG levels in all the groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of pro-opiomelanocortin-derived peptides on plasma levels of glucagon, insulin and glucose

Pro-opiomelanocortin (POMC) is a prohormone for several peptides including corticotropin, melanocyte stimulating hormones and beta-endorphin. POMC-derived peptides have been demonstrated in many tissues, including the hypothalamus and the endocrine pancreas, which play important roles in the control of plasma levels of glucagon, insulin and glucose. This article reviews the present knowledge concerning in vitro and in vivo effects of POMC-derived peptides on glucagon, insulin and glucose levels involving several possible mechanisms: direct effects on the endocrine pancreas (including endocrine, paracrine and peptidergic regulation) and glucose production, and indirect effects involving the hypothalamus, the autonomic nervous system and the adrenal gland.     

Plasma levels of immunoreactive ceruloplasmin and other acute phase proteins during lactation

Lactation elevates plasma copper as well as oxidase activity levels of the copper-containing, acute phase protein ceruloplasmin (Cp). The present study provides an initial inquiry into the mechanisms behind these changes. Plasma obtained from 12 lactating women, 1 month postpartum, displayed a greater percentage increase in immunoreactive Cp levels (mean increase = 89%) than in plasma copper (mean = 66%) or Cp oxidase activity (mean = 42%). Lactation did not increase plasma content of C-reactive protein or alpha 1-antitrypsin but significantly elevated haptoglobin concentrations. Plasma alpha 2-macroglobulin contents correlated with immunoreactive Cp levels in lactating women but not in controls. These results strengthen the hypothesis that plasma content of individual acute phase proteins is regulated by both overlapping and individualized processes. In addition, the present findings raise the possibility that lactation increases both Cp synthesis and plasma turnover time of Cp-bound copper.     

Dextrostix-Eyetone in the insulin hypoglycaemia test.

The Ames Dextrostix-Eyetone system was evaluated for monitoring the blood glucose concentration during insulin-induced hypoglycaemia. The results agreed well with laboratory values for plasma glucose, obtained by an orthotoluidine method, and the method was practicable as a bedside technique. In two cases quick results obtained with the Eyetone enabled the insulin tolerance test to be interrupted to prevent severe hypoglycaemia before the clinical indications were obvious. The extra time and effort required were minimal, and its value seems to far outweigh the disadvantage of the extra work entailed. Nevertheless, care in using the system was important, and the operator must familiarise himself with the system before the most reliable results can be obtained.     

Glucose, insulin and glucagon in the diabetic goose.

The relationships between plasma glucose, insulin and glucagon were studied in geese made diabetic by subtotal pancreatectomy. As early as the first hours after the operation, the plasma glucose increases and a permanent diabetes develops. This diabetic state is characterized by two features: a very low plasma insulin level, which does not vary during the survival of the diabetic animals and a concentration of plasma glucagon (of pancreatic origin) which transiently diminishes then rises far above the normal level, and is correlated with the basal concentration of plasma glucose. The impaired glucose tolerance observed in diabetic animals is related to the suppression of the glucose-insulin and glucose-glucagon feedback mechanisms.     

Rat corticotropin, insulin and thyroid hormone levels during the acute phase response to inflammation

Circulating levels of corticotropin, thyroid hormones and insulin were measured in rats at various times after turpentine-induced inflammation. Corticotropin increased rapidly showing a biphasic response with a four-fold increase at about 6-8 hr after inflammation and a 10-fold increase at 10 hr after inflammation. The response of insulin to inflammation was slower than corticotropin and the magnitude of the increase was smaller. Insulin increased by three-fold at 20 hr after inflammation. Thyroid hormone levels were depressed by turpentine inflammation. Levels fell after 4 hr and remained at low levels throughout. Administration of a cytokine preparation to rats also caused depressed thyroxine levels at short intervals after administration. However, levels increased at longer intervals after administration. This suggests that, like corticotropin and insulin, thyroid hormone levels could be under the control of immunotransmitters during the acute phase response.     

Pancreatic B-cell function in non-insulin-dependent diabetes mellitus during successive periods of sulfonylurea and insulin treatment: serum C-peptide response to glucagon and urine C-peptide excretion

Serum C-peptide responses to glucagon and daily urine C-peptide excretion in successive periods of different treatment in two groups of patients with non-insulin-dependent diabetes mellitus (NIDDM) (mean interval between two tests less than 1 month) were compared. In group A patients (n = 8), the glycemic control was improved after transferring the treatment from sulfonylurea (SU) to insulin (fasting plasma glucose: SU: 192 +/- 47, insulin: 127 +/- 21 mg/dl, mean +/- S.D., p less than 0.01). Fasting serum C-peptide immunoreactivity (CPR) was significantly lower at the period of insulin treatment (SU: 1.93 +/- 1.01, insulin: 1.47 +/- 0.79 ng/ml, p less than 0.05), but there was no difference in the increase in serum CPR (maximal--fasting) (delta serum CPR) during glucagon stimulation in the two periods of treatment (SU: 1.70 +/- 0.72, insulin: 1.47 +/- 0.98 ng/ml). In group B patients (n = 7), there was no significant difference in glycemic control after transferring the treatment from insulin to SU (fasting plasma glucose: insulin: 127 +/- 24, SU: 103 +/- 13 mg/dl). Fasting serum CPR was significantly lower during the period of insulin treatment (insulin: 1.39 +/- 0.64, SU: 2.21 +/- 0.86 ng/ml, p less than 0.025), but delta serum CPR during glucagon stimulation still showed no significant difference between the two periods (insulin: 1.97 +/- 1.16, SU: 2.33 +/- 1.57 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)