Glucose, insulin, pancreatic glucagon and glucagon-like immunoreactive materials in the plasma of normal and diabetic children. Effect of the initial insulin treatment.

Pancreatic glucagon (PG) and other glucagon-like immunoreactive materials (GLI) were measured in the plasma of normal and of newly diagnosed untreated diabetic children, using an antiglucagon serum (AGS) highly specific for pancreatic glucagon (AGS 18) and an AGS which crossreacts with extracts of intestinal mucosa (AGS 10). Gut GLI was considered to be the difference between "total" GLI (AGS 10) and PG (AGS 18). Glucose and immunoreactive insulin (IRI) were also measured. PG, total GLI and gut GLI were significantly elevated in children with severe insulin insufficiency and were reduced to normal by insulin treatment, even though a significant fasting hyperglycemia was still present. In three diabetic children who had high initial plasma IRI levels the three glucagon fractions were normal. We conclude that insulin insufficiency is characterized not only by high plasma levels of PG as previously reported, but also of gut GLI. These abnormalities can be corrected by the administration of insulin.     

The effect of long-distance running on plasma immunoreactive glucagon levels

Twelve highly conditioned long-distance runners were studied to determine the effects of marathon (42 km) and 10,000 m running on plasma immunoreactive glucagon (IRG), serum immunoreactive insulin (IRI), and serum glucose (G) levels. Blood samples were drawn just prior to and immediately upon completion of the run. Marathon running resulted in no significant change in G, IRI, or IRG levels. After running 10,000 m, plasma IRG levels did not change significantly, while IRI and G increased significantly. In evaluating the pooled data from both runs, a significant inverse correlation was observed between delta G and delta IRG. This relationship between delta G and delta IRG suggests that glucagon plays a role in maintaining normal blood glucose levels during strenuous exercise.     

Effect of acute ethanol load on postheparin plasma lipoprotein lipase and hepatic lipase activities and intravenous fat tolerance

This study aimed to examine the possibility that ethanol-induced rise of serum triglyceride concentration in man is partly due to an impaired removal of triglycerides from the circulation. Acute ethanol loads given to normal human subjects after an overnight fast reduced the postheparin plasma lipoprotein lipase activity by an average of 25% but did not influence the postheparin plasma hepatic lipase activity or fractional removal of Intralipid triglyceride. When alcolhol was administered to fed subjects in the evening the postheparin plasma hepatic lipase was significantly decreased in the next morning as compared to corresponding control value but the lipoprotein lipase and Intralipid clearance were not changed. It is concluded that the slight decrease of lipoprotein lipase during alcohol intoxication may contribute to the hyperlipemic effect of ethanol.     

Studies on submaxillary gland immunoreactive glucagon.

Biologically active immunoreactive glucagon is present in submaxillary gland of rat, mouse, guinea pig and human and can be extracted by saline adjusted to pH 2.8 with HCl. Chromatography on Sephadex G-150 indicates its molecular weight to be 29,000. It has similar immunologic characteristics as pancreatic glucagon. It is biologically active and elevates plasma glucose and insulin when injected intraperitoneally into rats. Compared to pancreatic glucagon, the hyperglycemic effect persists much longer. It competes with pancreatic glucagon for binding to specific glucagon receptors of rat liver plasma membranes. It is stable to pH changes, however, urea dissociates it into several smaller molecular weight fragments including that of 3500. It appears to be an aggregate of smaller glucagon molecules and is not responsible for immunoreactive glucagon in totally eviscerated rats. $\text{In vitro}$, the submaxillary gland does not release immunoreactive glucagon in response to arginine or glucose.     

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 acute and chronic endotoxin treatment on glucagon and insulin receptors on rat liver plasma membranes

The effects of acute and chronic endotoxin treatment on the plasma levels of insulin and glucagon and their binding to rat liver plasma membranes were examined. Both acute and chronic endotoxin administration increased plasma glucagon levels and decreased the glucagon to insulin molar ratio. Acute, but not chronic, endotoxin decreased blood glucose and insulin levels. Glucagon binding was increased in membranes prepared from the acutely treated rats. However, in membranes obtained from rats treated chronically with endotoxin, only insulin binding was increased. The increases in the binding of both insulin and glucagon were the result of increases in receptor sites.     

The effect of temperature on immunoreactive glucagon plasma level in carp Cyprinus carpio

Plasma immunoreactive glucagon levels (IRG), plasma glucose levels and brain and liver glycogen concentrations were analyzed in carp (adapted to 15 degrees C) subjected to short-term temperature changes (1.6 or 11 h, at 5 degrees C or 28 degrees C, respectively) and to long-term temperature changes (21 months at 28 degrees C). The high temperature (28 degrees C) produced significant increases in IRG in both short and long-term experiments. Brain glycogen also decreased in both experiments whereas liver glycogen only changed in the long-term experiment. Low temperatures did not provoke any changes either in IRG or in liver glycogen, whereas brain glycogen decreased in the 1 h exposure. In short, under these conditions in carp, IRG did not respond to low temperature but could play an important role in high temperature acclimation.     

The effect of glucagon antibodies on plasma glucose and insulin levels

The actions of glucagon and insulin are interrelated as the two hormones have opposite physiological effects and the secretion of insulin is regulated, at least in part, by the level of glucagon. We have found that rabbits which are immunized against glucagon have normal fasting levels of blood glucose but a lowered level of insulin. These rabbits are also able to rapidly utilize intravenously injected glucose butwith a much lower plasma level of insulin. These results demonstrate that in the presence of glucagon antibodies, normal blood sugar levels can be maintained with a reduced supply of insulin. It is suggested that this finding may be useful in the treatment of diabetes.     

Plasma insulin concentration during physiological variations in immunoreactive plasma secretin.

The effect of endogenous and exogenous secretin on fasting plasma insulin and glucose concentrations in peripheral venous blood was studied. In 10 non-diabetic subjects intragastric instillation of 300 ml 0.1 mol/l hydrochloric acid increased the plasma secretin concentration significantly. This increment did not influence insulin or glucose concentration. Control experiments with intragastric instillation of 300 ml of isotonic saline did not influence the plasma concentration of secretin, insulin or glucose. In four other non-diabetic persons no significant changes were found in plasma insulin or glucose concentration during an i.v. infusion of pure natural porcine secretin in doses of 0.1, 0.3, 1.0 and 3.0 clinical units/kg/h. The results suggest that secretin is without effect on insulin secretion in the fasting normal subject.     

Effect of glucagon on insulin receptor phosphorylation in intact liver cells.

Evidence is presented that incubation of rat liver cells with glucagon leads to an increase in the phosphorylation of specific serine residues within insulin receptors, particularly in the presence of insulin. However, no changes in either the tyrosine phosphorylation of the receptors or the tyrosine kinase activity towards a synthetic peptide substrate was detected.     

Effect of alrestatin on arginine-induced secretion of glucagon and insulin in the rat.

Alrestatin, a lens aldose reductase inhibitor, decreased i.v. arginine-induced glucagon levels and augmented arginine-stimulated insulin release in the ether anesthetized rat. Alrestatin may then be useful in the treatment of diabetes mellitus, due to its actions on insulin and glucagon, and its capacity to delay the onset of sugar-induced cataracts in the rat.