Pancreatic-Glucagon-Like Immunoreagtivity After Intravenous Insulin in Normals and Chronic-Pancreatitis Patients

151

A B S T R A C T In order to characterize the influence of the adrenergic system on pancreatic glucagon secretion in man, changes in basal glucagon secretion during infusions of pure alpha and beta adrenergic agonists and their specific antagonists were studied. During infusion of isoproterenol (3 Ag/min), a beta adrenergic agonist, plasma glucagon rose from a mean (±SE) basal level of 104±10 to 171±15 pg/ml, P < 0.0002. Concomitant infusion of propranolol (80 Ag/min), a beta adrenergic antagonist, prevented the effects of isoproterenol, although propranolol itself had no effect on basal glucagon secretion. During infusion of methoxamine (0.5 mg/ min), an alpha adrenergic agonist, plasma glucagon declined from a mean basal level of 122±15 to 75±17 pg/ml, P <0.001. Infusion of phentolamine (0.5 mg/ min), an alpha adrenergic antagonist, caused a rise in plasma glucagon from a mean basal level of 118±16 to 175+21 pg/ml, P <0.0001. Concomitant infusion of methoxamine with phentolamine caused a reversal of the effects of phentolamine.The present studies thus confirm that catecholamines affect glucagon secretion in man and demonstrate that the pancreatic alpha cell possesses both alpha and beta adrenergic receptors. Beta adrenergic stimulation augments basal glucagon secretion, while alpha adrenergic stimulation diminishes basal glucagon secretion. Furthermore, since infusion of phentolamine, an alpha adrenergic antagonist, resulted in an elevation of basal plasma glucagon levels, there appears to be an inhibitory alpha adrenergic tone governing basal glucagon secretion. The above findings suggest that catecholamines may influence glucose homeostasis in man through their effects on both pancreatic alpha and beta cell function.

Section: Resultsmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Adrenergic Modulation of Pancreatic Glucagon Secretion in Man

Gerich¹,

Langlois²,

Noacco³

et al. 1974

151

“…At low glucose levels, glucagon secretion is enhanced and at higher levels suppressed. This has been demonstrated both in vivo (1)(2)(3)(4)(5)(6)(7)(8)(9) and in vitro (10)(11)(12)(13)(14)(15). The details of the timing and magnitude of glucagon release in response to varying glucose concentrations remain incompletely defined.…”

Section: Introductionmentioning

confidence: 86%

Glucagon Secretion from the Perfused Rat Pancreas STUDIES WITH GLUCOSE AND CATECHOLAMINES

Weir¹,

Knowlton²,

Martin³

1974

116

A B S T R A C T The isolated in situ perfused rat pancreas was used to study glucose and catecholamine control of glucagon secretion, and to investigate the possible role of endogenous cyclic AMP as a mediator of this secretory process. When perfusate glucose was acutely dropped from 100 to 25 mg/100 ml, glucagon was released in a biphasic pattern with an early spike and a later plateau-like response. 300 mg/100 ml glucose suppressed glucagon secretion to near the detection limit of the radioimmunoassay (15 pg/ml). When perfusate glucose was dropped from 300 to 25 mg/100 ml, a delayed, relatively small peak occurred suggesting persisting alpha cell suppression by prior high glucose exposure. 2-Deoxy d-glucose stimulated glucagon secretion and inhibited insulin secretion.Glucagon was secreted in a biphasic pattern in response to both 2.7 X 10-M epinephrine and norepinephrine. The glucagon response to epinephrine was markedly suppressed by glucose at 300 mg/100 ml, and the biphasic response pattern was obliterated. Glucose evoked a two-phase insulin secretory pattern, and the second phase was markedly and rapidly inhibited by epinephrine. Pancreases were perfused with glucose at 300 mg/100 ml which was then lowered to 80 mg/100 ml. 5 min later, epinephrine was infused and definite blunting of the first-phase spike occurred. 10 mM theophylline produced modest rapid uniphasic stimulation of glucagon release, and, in addition, caused enhancement of epinephrine-stimulated glucagon release.An inhibitory influence upon epinephrine-stimulated glucagon was observed as well. Insulin secretion was stimulated by 10 mM theophylline, and this stimulation was inhibited by epinephrine.

“…In man, both enhanced glucagon release and activation of the sympathetic nervous system are sequels of starvation and insulin-induced hypoglycemia (16)(17)(18)(19)(20)(21)(22)(23); therefore, the present investigations were designed to determine whether the increases in plasma glucagon levels under these circumstances were influenced by alpha or beta adrenergic blockade. In addition, these studies also examined the possibility of a circadian rhythm in glucagon release during fasting.…”

Section: Introductionmentioning

confidence: 99%

The Effect of Adrenergic Blockade on the Glucagon Responses to Starvation and Hypoglycemia in Man

Walter¹,

Dudl²,

Palmer³

et al. 1974

110

ABSTRA CT In an attempt to ascertain whether the sympathetic nervous system modulates glucagon release in man during starvation and hypoglycemia, the influence of alpha and beta adrenergic blockade on glucagon responses was studied in young, healthy men subjected to fasting and insulin-induced hypoglycemia. Six volunteers fasted for 84 h on three separate occasions. Plasma immunoreactive glucagon (IRG), measured initially at 12 h, climbed gradually from mean levels of 54 pg/ml to a zenith of 124 pg/ml at 48 h, with maintenance of these levels for the duration of the fast. The infusion of propranolol or phentolamine throughout the terminal 24 h of the second and third fasts failed to alter the pattern of IRG release. After an overnight fast, five volunteers received insulin intravenously, which evoked a mean rise in plasma IRG levels from 63 pg/ml to a maximum of 256 pg/ml at 30 min. The concurrent administration of propranolol or phentolamine did not modify the glucagon responses to insulin-induced hypoglycemia. These data suggest that the augmented glucagon release in man during starvation or after hypoglycemia is not significantly regulated by signals from the adrenergic nervous system.