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Biomedical subjects

P L Werner

Publications and source records attributed to P L Werner.

12 recordsLinked to original sources
PubMed1983

Autonomic nervous system control of glucagon secretion during neuroglucopenia.

The role which the autonomic nervous system (ANS) plays in controlling glucagon (IRG) secretion is controversial. Strong activation of the ANS was achieved in baboons with 500 mg/kg 2-deoxyglucose, producing a 20-fold rise in epinephrine and a 15-fold rise in IRG. Under such circumstances, the IRG response was attenuated by both alpha- and beta-adrenergic blockade, strongly suggesting that this part of the IRG rise post 2-deoxyglucose was mediated via adrenergic mechanisms. The baboon is similar to man, with the sympatho-adrenal axis having little influence on IRG secretion during mild activation of the ANS. However, during stronger ANS activation with 2-deoxyglucose, a clear effect of the sympatho-adrenal axis on IRG secretion was demonstrated. Whether experiments in primates demonstrate an effect of the ANS on IRG secretion may depend primarily on the strength of the neural response elicted.

Animals↗
PubMed1980

Comparison of glucagon responses to 2-deoxy-D-glucose and hypoglycemia in man.

2-Deoxy-D-glucose (2DG), by competitive inhibition of glucose utilization, produces a state of intracellular glucopenia with resultant activation of both the sympathetic and parasympathetic branches of the autonomic nervous system. We have investigated the relationship between the activation of the autonomic nervous system caused by this drug and glucagon secretion. Subjects experienced symptoms identical to those observed during true hypoglycemia and demonstrated a marked rise in both gastric acid secretion and urinary epinephrine excretion. Mean immunoreactive glucagon (IRG) levels rose only slightly post-2DG (maximal mean increment, 18 pg/ml). Insulin-induced hypoglycemia, although eliciting a similar increase in urinary epinephrine excretion, was followed by a severalfold increase in IRG. Thus, although hypoglycemia and 2DG induced similar discharge of the autonomic nervous system, the glucagon response to hypoglycemia was much greater. These observations provide strong evidence that marked increases in sympathetic and parasympathetic discharge in man are weak alpha-cell stimuli and further support the hypothesis that the rise in IRG that occurs during hypoglycemia is not mediated primarily via the autonomic nervous system.

Adult↗
PubMed1979

Differential effect of isoproterenol on acute glucagon and insulin release in man.

In man, the infusion of arginine or isoproterenol elevates immunoreactive glucagon and insulin levels. Since arginine administered as a pulse stimulates the acute secretion of both hormones, and an insulin rise is observed after the bolus injection of isoproterenol, these findings probably represent a direct effect of arginine and isoproterenol on islet cells. To determine if there is an acute alpha-cell response to isoproterenol, we have administered this beta-adrenergic agonist as a bolus to healthy volunteers. Arginine administered as a pulse elicited both insulin and glucagon responses whereas pulses of isoproterenol, at half maximal and maximal insulin-stimulating doses, had little effect on glucagon levels. This relative insensitivity of the alpha cells to stimulation by isoproterenol suggests that endogenous beta-adrenergic tone may have a stronger influence on insulin than on glucagon secretion. Furthermore, these findings raise the possibility that beta-adrenergic regulation of plasma glucagon levels in vivo occurs by an indirect mechanism rather than a direct effect on the alpha cells.

Arginine↗
PubMed1979

Evaluation of the control of glucagon secretion by the parasympathetic nervous system in man.

To evaluate the influence of the parasympathetic nervous system on human glucagon secretion, we have measured the plasma immunoreactive glucagon (IRG) levels after the administration of edrophonium, bethanechol chloride, and 2-deoxyglucose, and have compared the IRG responses to hypoglycemia in normal, atropinized, and vagotomized man. Edrophonium administered i.v. and bethanechol chloride administered s.c. did not affect IRG levels. Two-deoxy-glucose resulted in symptomatic neuroglucopenia with resultant vagal discharge, as evidenced by increased gastric acid secretion; but no changes in IRG concentrations were observed. The IRG response to insulin-induced hypoglycemia in normal subjects was not influenced by the administration of atropine. In seven subjects with a truncal vagotomy and no increased gastric acid secretion during insulin-induced hypoglycemia, the IRG increases were indistinguishable from those of control subjects in terms of timing, peak level obtained, or total glucagon response. We conclude that the cholinergic system is unlikely to play an important role in modulating glucagon secretion in man.

Adult↗
PubMed1978

Dominant inheritance of large molecular weight immunoreactive glucagon.

Plasma from some individuals contains substances which are reactive with glucagon antiserum, are larger than 3,500-dalton glucagon, and have been proposed as possible precursors of glucagon. We have evaluated three generations of a kindred in which 9 of 15 members evaluated had elevated plasma levels of large molecular weight immunoreactive glucagon (L-IRG) with an average concentration of 822 pg/ml. The distribution of individuals with elevated L-IRG levels in this pedigree is consistent with autosomal dominant inheritance. Gel filtration of plasma revealed that all affected family members had excessive amounts of two L-IRG peaks, one with a molecular weight of approximately 9,000 daltons and another in the 10,000 to 20,000-dalton range. Oral glucose tolerance tests were nondiabetic and elicited a fall in L-IRG levels, whereas L-IRG concentrations rose dramatically during the infusion of arginine. These L-IRG species may be precursors of 3,500-DALTON GLUCAGON AND MAY BE ELEVATED in this kindred because of an inherited defect in either their synthesis or degradation.

Adolescent↗
PubMed1978

Immunoreactive glucagon responses to oral glucose, insulin infusion and deprivation, and somatostatin in pancreatectomized man.

In a group of pancreatectomized subjects, immunoreactive glucagon (IRG) concentrations were normal after an overnight fast, increased after oral glucose, were not suppressed by somatostatin (SRIF) or insulin, and in two of four subjects they rose with an arginine infusion. Even though the SRIF infusion failed to lower IRG, there was a fall in plasma glucose concentration in both subjects. In two subjects, endogenous hyperglycemia occurred during insulin withdrawal without a rise in IRG, and, in one subject, mild diabetic ketoacidosis developed with only a minimal rise in IRG. These results support the presence of an extrapancreatic source of IRG in man. Secretion from these extrapancreatic alpha cells appears to be regulated differently than secretion from pancreatic alpha cells.

Adult↗
PubMed1977

Glucagon and catecholamine secretion during hypoglycemia in normal and diabetic man.

To examine the role of catecholamines in glucopenia-induced glucagon secretion, urinary epinephrine and norepinephrine and plasma immunoreactive glucagon (IRG) were measured during insulin-induced hypoglycemia in normal and insulin-dependent diabetic-man. Despite equivalent levels of hypoglycemia the mean plasma IRG increment in diabetes was only 15% of normals. The increases in epinephrine and norepinephrine were comparable in diabetics and normals; thus, the blunted response in plasma IRG to the stimulus of low blood sugar in diabetics cannot be explained by a generalized defect in catecholamine secretion. It is suggested that an alpha-cell glucoreceptor defect may account for the abnormal response to glucopenia in diabetics. To evaluate the possibility that impaired sensitivity to circulating catecholamines could explain the alpha cell dysfunction in diabetics, exogenous epinephrine was infused in normals and insulin-dependent diabetics. Elevated plasma IRG during epinephrine infusion was observed in only 50% of normals. The diabetics were hyperresponsive; mean increment in plasma IRG 3 times that of normals. The data demonstrate enhanced rather than impaired sensitivity to catecholamines in diabetes mellitus.

Adolescent↗