Charles C. Gale

Somatostatin: Hypothalamic Inhibitor of the Endocrine Pancreas

Somatostatin, a hypothalamic peptide that inhibits the secretion of pituitary growth hormone, inhibits basal insulin secretion in fasted cats and rats. In fasted baboons both basal and arginine-stimulated secretion of insulin and glucagon are inhibited. Somatostatin appears to act directly on the endocrine pancreas. The action is dose-related, rapid in onset, and readily reversed.

Central α-Adrenergic Regulation of Growth Hormone and Insulin

Serum growth hormone (GH) fell and serum insulin (IRI) rose within 30 min following infusion of phentolamine, an α-adrenergic blocking agent, into the anterior hypothalamus or third ventricle of conscious, fasted baboons. GH and IRI were unchanged following intravenous infusion systemically of phentolamine at doses 2 to 4 times greater than given centrally, indicating that the reciprocal changes in GH and IRI did not result from direct action of phentolamine on the adenohypophysis and pancreatic islets. Rather, these data suggest that the phentolamine blocked hypothalamic adrenergic mechanisms participating in the normal regulation of GH and IRI. Plasma glucose and 17-OHCS rose and plasma glycerol fell in association with changes in GH and IRI, but blood pressure, heart rate and internal temperature were not altered.

Studies of substrate regulation in fasting: II. Effect of infusion of glucose into the carotid artery upon fasting lipolysis in the baboon

The effect of glucose infusion on rates of lipolysis were studied in a group of chair-trained papio baboons that had been prepared for chronic intravenous and intracarotid infusion. All studies were carried out after a 24 hr period of fasting and when the animals were fully awake. After a control interval of 1 hr, a glucose infusion was begun either intravenously or intra-arterially. The infusion was continued at a constant rate for 2 hr and then changed directly to the alternate route and continued an additional 2 hr. Blood samples were collected at 30-min intervals for glucose, free fatty acid (FFA), glycerol, insulin, and in some studies, growth hormone (GH) determination. When glucose doses less than 0.5 mg/kg per min were used, no change in the products of lipolysis was noted during either venous or carotid administration, and glucose and insulin levels remained stable or fell gradually. With doses of glucose between 0.5 and 0.6 mg/kg per min, a greater fall in both FFA and glycerol was noted during carotid administration. No definite changes in plasma glucose or insulin levels were noted during either infusion period. These changes in lipolysis were noted regardless of the sequence of infusion, and a similar differential suppression of FFA was noted during a 24 hr period of carotid glucose administration. When doses of glucose larger than 0.6 mg/kg per min were used, inhibition of lipolysis was noted during both phases of infusion. No definite change in GH levels was noted during the periods of fasting, and the levels of the hormone did not appear to be related to changes in glucose, insulin, or FFA levels. These data provide additional evidence for the presence in the central nervous system of a glucose-sensitive center which alters lipolytic rates independently of insulin and GH, probably by altering sympathetic tone to adipose tissue.

Noradrenergic and Dopaminergic Regulation of GH and Prolactin in Baboons

Aminergic regulation of growth hormone (GH) and prolactin (Prl) was studied in male adolescent baboons by i.v. infusion of dopamine (DA), norepinephrine (NE), thyrotropin-releasing hormone (TRH), phentolamine, haloperidol, and inhibitors of DA-beta-hydroxylase and peripheral decarboxylase. 20-min infusion of DA (40 microgram/kg.min) and 60-min infusion of NE (0.4 microgram/kg.min) stimulated GH release. The DA-induced GH release was suppressed by concomitant infusion of FLA 63 (inhibitor of NE synthesis from DA) and by phentolamine, indicating alpha-adrenergic mediation of GH release. Microinfection of DA (0.8 microgram/kg) into the medial basal hypothalamus (MBH) lowered basal GH. Prl was released by i.v. TRH, and this effect was suppressed by i.v. DA but not by i.v. NE. Blockade of peripheral decarboxylase by carbidopa elicited a marked and sustained rise in Prl which was inhibited by i.v. DA. Microinjection of NE (0.8 microgram/kg) into the MBH released Prl. These data indicate that in the MBH, alpha-adrenergic mechanisms release GH and Prl, and that dopaminergic mechanisms suppres GH.

Hormone Fuel Interrelationships During Alcohol Hypoglycemia in Man

Summary Basal serum immunoreactive insulin (IRI) levels fell promptly and in parallel with the decline observed in circulating glucose levels when alcohol was administered intravenously to fasting man. Hypoglycemia and the decrease in basal insulin secretion were associated with an initial transient increment in growth hormone levels and sustained lipolysis manifested by increased free fatty acid, glycerol and acetoacetate concentrations. These findings may result from activation of the sympathetic nervous system which is known to be operative in other hypoglycemic states.

Plasma Growth Hormone in the Infant Undergoing Deep Hypothermic Cardiovascular Surgery

Summary and Conclusions A study of plasma growth hormone and glucose, and body temperature, was conducted in six infants undergoing deep hypothermic cardiovascular surgery. Pronounced hyperglycemia occurred during hypothermia when the infants received exogenous glucose, confirming earlier reports of diminished plasma glucose utilization at low body temperatures. Although growth hormone levels were high during ether anesthesia, they fell or changed little with cooling, and did not appear related to core temperature or to plasma glucose concentration. These findings indicate that changes in growth hormone levels in operated hypothermic infants did not relate to cold stress, alterations in plasma glucose concentration, or diminished glucose utilization.

A model of sustained activation of the symphatetic nervous system (SNS) using anterior hypothalamic cooling in the baboon

Abstract A model has been developed to simulate central activation of the sympathetic nervous system (SNS) in unanesthetized baboons. By continuously cooling the preoptic anterior hypothalamus with an implanted thermode, a chronic heat production response is generated. In the primate, SNS activation is a major feature of the response to cold stress. During central cooling, oxygen consumption and catecholamine excretion doubled. These responses have been sustained for 30 days. Metabolic and endocrine changes accompanying chronic SNS activation include (1) an early period of basal hyperinsulinemia followed by restoration of normal insulin sensitivity, (2) an unexpected maintenance of normal (or even increased) responsiveness to isoproterenol (heart rate, insulin secretion and lipolysis, (3) increased glucagon levels throughout, (4) a persistent and progressive fall in T3 without change in T4 which was not explained by decreased food intake since this did not diminish, and weight was maintained. The model may prove useful in characterizing the adaptations and maladaptations which accompany sustained increases in central SNS activity in primates.