Basal insulin, glucagon, and growth hormone replacement

2007 ◽  
Vol 293 (5) ◽  
pp. E1303-E1310 ◽  
Author(s):  
Suzanne M. Breckenridge ◽  
Bharathi Raju ◽  
Ana Maria Arbelaez ◽  
Bruce W. Patterson ◽  
Benjamin A. Cooperberg ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Plasma Glucose ◽  
Hormone Replacement ◽  
Insulin Dose ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Glucose Production ◽  
Complete Suppression ◽  
Glucose Levels ◽  
Clamp Technique

Conclusions drawn from the pancreatic (or islet) clamp technique (suppression of endogenous insulin, glucagon, and growth hormone secretion with somatostatin and replacement of basal hormone levels by intravenous infusion) are critically dependent on the biological appropriateness of the selected doses of the replaced hormones. To assess the appropriateness of representative doses we infused saline alone, insulin (initially 0.20 mU·kg−1·min−1) alone, glucagon (1.0 ng·kg−1·min−1) alone, and growth hormone (3.0 ng·kg−1·min−1) alone intravenously for 4 h in 13 healthy individuals. That dose of insulin raised plasma insulin concentrations approximately threefold, suppressed glucose production, and drove plasma glucose concentrations down to subphysiological levels (65 ± 3 mg/dl, P < 0.0001 vs. saline), resulting in nearly complete suppression of insulin secretion ( P < 0.0001) and stimulation of glucagon ( P = 0.0059) and epinephrine ( P = 0.0009) secretion. An insulin dose of 0.15 mU·kg−1·min−1 caused similar effects, but a dose of 0.10 mU·kg−1·min−1 did not. The glucagon and growth hormone infusions did not alter plasma glucose levels or those of glucoregulatory factors. Thus, insulin “replacement” doses of 0.20 and even 0.15 mU·kg−1·min−1 are excessive, and conclusions drawn from the pancreatic clamp technique using such doses may need to be reassessed.

Demonstration of a role for growth hormone in glucose counterregulation

1989 ◽  
Vol 256 (6) ◽  
pp. E835-E843 ◽  
Author(s):  
P. De Feo ◽  
G. Perriello ◽  
E. Torlone ◽  
M. M. Ventura ◽  
F. Santeusanio ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Plasma Glucose ◽  
Glucose Utilization ◽  
Hepatic Glucose Production ◽  
Hormone Secretion ◽  
Plasma Catecholamines ◽  
Growth Hormone Secretion ◽  
Glucose Production ◽  
Plasma Free Fatty Acid ◽  
Normal Subjects

To test the hypothesis that growth hormone secretion plays a counterregulatory role in prolonged hypoglycemia in humans, four studies were performed in nine normal subjects. Insulin (15 mU.M-2.min-1) was infused subcutaneously (plasma insulin 27 +/- 2 microU/ml), and plasma glucose decreased from 88 +/- 2 to 53 +/- 1 mg/dl for 12 h. In study 1, plasma glucose, glucose fluxes (D-[3-3H]glucose), substrate, and counterregulatory hormone concentrations were simply monitored. In study 2 (pituitary-adrenal-pancreatic clamp), insulin and counterregulatory hormone secretions (except for catecholamines) were prevented by somatostatin (0.5 mg/h iv) and metyrapone (0.5 g/4 h po), and glucagon, cortisol, and growth hormone were reinfused to reproduce the concentrations of study 1. In study 3 (lack of growth hormone increase), the pituitary-adrenal-pancreatic clamp was performed with maintenance of plasma growth hormone at basal levels, and glucose was infused whenever needed to reproduce plasma glucose concentration of study 2. Study 4 was identical to study 3, but exogenous glucose was not infused. Isolated lack of a growth hormone response caused a decrease in hepatic glucose production and an increase in glucose utilization that resulted in an approximately 25% greater hypoglycemia despite compensatory increases in plasma catecholamines. Plasma free fatty acid, 3-beta-hydroxybutyrate, and glycerol concentrations were reduced approximately 50%. It is concluded that growth hormone normally plays an important counterregulatory role during hypoglycemia by augmenting glucose production, decreasing glucose utilization, and accelerating lipolysis.

Insulin hypoglycemia and growth hormone secretion in sheep: a paradox revisited

1999 ◽  
Vol 277 (2) ◽  
pp. E253-E258 ◽  
Author(s):  
Craig A. Jaffe ◽  
Bryan W. Huffman ◽  
Roberta Demott-Friberg
Keyword(s):  
Growth Hormone ◽  
Insulin Dose ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Insulin Administration ◽  
Insulin Hypoglycemia ◽  
Fed State ◽  
Gh Secretion ◽  
Baseline Concentrations

Although insulin-induced hypoglycemia is a potent stimulus for growth hormone (GH) secretion in humans, hypoglycemia was reported to suppress GH in sheep. We investigated whether GH suppression in sheep during insulin hypoglycemia resulted from the dose of insulin administered or the fed state of the animal. Saline or insulin (0.05, 0.2, 1.0, or 5.0 U/kg) intravenous boluses were administered to eight fasted ewes in a crossover experiment. In another experiment, four sheep were fed 2 h before intravenous administrations of either 0.2 or 5 U/kg of insulin. All doses of insulin resulted in comparable hypoglycemia, although the duration of hypoglycemia increased directly with insulin dose. Hypoglycemia in fasted animals stimulated GH secretion. The GH rise above baseline was inversely related to the insulin dose, and the insulin doses of 1 and 5 U/kg resulted in late suppression of GH below baseline concentrations. Insulin administration to fed animals caused an identical degree of hypoglycemia but no increase in GH. Insulin-hypoglycemia stimulates GH secretion in sheep in a manner similar to humans, and the response is dependent on both fed state and insulin dose.

Hierarchy of glycemic thresholds for counterregulatory hormone secretion, symptoms, and cerebral dysfunction

1991 ◽  
Vol 260 (1) ◽  
pp. E67-E74 ◽  
Author(s):  
A. Mitrakou ◽  
C. Ryan ◽  
T. Veneman ◽  
M. Mokan ◽  
T. Jenssen ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Plasma Glucose ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Cerebral Function ◽  
Blurred Vision ◽  
Autonomic Symptoms ◽  
Glucose Levels ◽  
Cerebral Dysfunction ◽  
Glucose Clamp Technique

To define glycemic thresholds for activation of counterregulatory hormone secretion, initiation of symptoms (autonomic and neuroglycopenic), and onset of deterioration of cognitive function, we measured indexes of these responses during glycemic plateaus of 90, 78, 66, 54, and 42 mg/dl in 10 normal volunteers, with the use of the hyperinsulinemic glucose clamp technique. Activation of glucagon, epinephrine, norepinephrine, and growth hormone secretion began at arterialized venous plasma glucose concentrations of 68 +/- 1, 68 +/- 1, 65 +/- 1, and 67 +/- 2 (SE) mg/dl, respectively. Autonomic symptoms (anxiety, palpitations, sweating, irritability, and tremor) began at 58 +/- 2 mg/dl, which was significantly (P = 0.0001) lower. Neuroglycopenic symptoms (hunger, dizziness, tingling, blurred vision, difficulty thinking, and faintness) and deterioration in cognitive function tests began at 51 +/- 3 and 49 +/- 2 mg/dl, respectively, values that were both significantly (P = 0.018 and 0.004, respectively) lower than that for initiation of autonomic symptoms. We therefore conclude that there is a distinct hierarchy of responses to decrements in plasma glucose, such that the threshold for activation of counterregulatory hormone secretion occurs at higher plasma glucose levels than that for initiation of autonomic warning symptoms, which in turn occurs at higher plasma glucose levels than that for onset of neuroglycopenic symptoms and deterioration in cerebral function. Such a hierarchy would maximize the opportunity to avoid incapacitating hypoglycemia.

Effects of glucose load and/or arginine on insulin and growth hormone secretion in hyperprolactinemia and obesity

1996 ◽  
Vol 135 (2) ◽  
pp. 205-210 ◽  
Author(s):  
Mauro Maccario ◽  
Silvia Grottoli ◽  
Paola Razzore ◽  
Massimo Procopio ◽  
Salvatore Endrio Oleandri ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Growth Hormone ◽  
Insulin Secretion ◽  
Body Mass ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Insulin Response ◽  
Glucose Load ◽  
Gh Secretion ◽  
Glucose Levels

Maccario M, Grottoli S, Razzore P, Procopio M, Oleandri SE, Ciccarelli E, Camanni F, Ghigo E. Effects of glucose load and/or arginine on insulin and growth hormone secretion in hyperprolactinemia and obesity. Eur J Endocrinol 1996;135:205–10. ISSN 0804–4643 In hyperprolactinemic patients an exaggerated glucose-induced insulin secretion has been reported, but these results have not been confirmed by other researchers. On the other hand, there are few data concerning somatotrope secretion in this condition. In order to clarify these points, in seven normal weight hyperprolactinemic female patients (HP: age 18–46 years, body mass index = 21.8 ± 0.6 kg/m2, basal prolactin = 91.7 ± 16.5 μg/l) we studied the effects of glucose load (100 g orally) and/or arginine (0.5 g/kg infused over 30 min on insulin glucose and growth hormone (GH) levels. These results were compared with those obtained in seven patients with simple obesity (OB: age 23–48 years, body mass index = 38.3 ± 2.6 kg/m2) in whom exaggerated insulin and low GH secretion are well known. Seven normal women (NS: age 26–32 years, body mass index = 20.6 ± 1.9 kg/m2) were studied as controls. The insulin response to glucose in HP (area under curve = 11460.8 ± 1407.5 mU·min·1−1) was not significantly different from NS (7743.7 ±882.9 mU·min·1−1) and OB (14 504.8 ± 1659.9 mU·min·1−1). The arginine-induced insulin release in HP and OB was similar (4219.4 ± 631.7 and 4107.3 ± 643.2 mU·min·1−1. respectively), both being higher (p < 0.02) than in NS (2178.1 ± 290.9 mU·min·1−1). Glucose and arginine had an additive effect on insulin release in HP and NS (19 769.1 ± 3249.6 and 10996.6 ± 1201.0 mU·min·1−1, respectively) and a synergistic effect in OB (28117.3± 5224.7 mU·min·1−1). In HP the insulin response to the combined administration of glucose and arginine was not significantly different from the one in OB, and both were higher (p < 0.05) than in NS. The increase in glucose levels after glucose administered on its own or combined with arginine was higher (p < 0.02) and longer lasting in OB than in NS and HP. After arginine in OB, the glucose levels did not show the late decrease under baseline values observed in HP and NS. Glucose inhibited GH secretion both in HP and NS (p < 0.05), while arginine stimulated it in all groups, although the GH response in HP and NS was higher (p < 0.03) than in OB. The arginine-induced GH secretion was inhibited by glucose in HP and NS but not in OB. These results demonstrate that both in hyperprolactinemic patients and in obesity there is a clear increase in insulin secretion. The insulin hyperresponsiveness in hyperprolactinemia is more clearly demonstrated by combined stimulation with glucose and arginine. In spite of similar insulin hypersecretion in hyperprolactinemic and obese patients, GH secretion is reduced only in the latter; with these data the hypothesis that somatotrope insufficiency in obesity is due to hyperinsulinism is unlikely. Ezio Ghigo, Divisione di Endocrinologia, Ospedale Molinette, C.so Dogliotti 14, 10126 Torino, Italy

Insulin, glucagon, and catecholamines in prevention of hypoglycemia during fasting

1989 ◽  
Vol 256 (5) ◽  
pp. E651-E661 ◽  
Author(s):  
P. J. Boyle ◽  
S. D. Shah ◽  
P. E. Cryer
Keyword(s):  
Growth Hormone ◽  
Plasma Glucose ◽  
Hormone Replacement ◽  
Glucose Production ◽  
Base Line ◽  
Adrenergic Blockade ◽  
Plasma Glucagon ◽  
Prolonged Fasting ◽  
Glucose Clearance ◽  
Normal Humans

To dissect the mechanisms of the prevention of hypoglycemia during fasting, eight normal humans were studied after overnight and 3-day fasts. Prolonged fasting resulted in the expected decrements in base-line glucose production and plasma glucose, insulin, and C-peptide and increments in plasma glucagon, epinephrine, norepinephrine, growth hormone, and cortisol. After the overnight and 3-day fasts, insulin restoration (0.2 mU.kg-1.min-1) alone resulted in transient decrements in glucose production and only 15 and 19% decrements in plasma glucose, respectively. Selective glucagon deficiency (somatostatin infusion with insulin and growth hormone replacement) resulted in transient decrements in glucose production and additional 24 and 29% decrements in plasma glucose, respectively. Notably, plasma glucose plateaued under both fasting conditions in both instances. Combined alpha- and beta-adrenergic blockade (phentolamine and propranolol infusions) alone had no effect on glycemia under either fasting condition. However, progressive hypoglycemia developed during adrenergic blockade coupled with glucagon deficiency after the overnight fast (85 +/- 2 to 48 +/- 4 mg/dl, P less than 0.001) and after the 3-day fast (65 +/- 2 to 33 +/- 1 mg/dl, P less than 0.001). These were the result of both decrements in glucose production and increments in glucose clearance. Thus we conclude that during fasting 1) the prevention of hypoglycemia is not due solely to decreased insulin secretion. 2) Glucagon plays a primary counterregulatory role. Sympathochromaffin catecholamines are not normally critical but compensate and become critical when glucagon is deficient. Adrenomedullary epinephrine is probably the relevant catecholamine. 3) Other hormones, neurotransmitters, or substrate effects may, or may not, be involved; if they are, they appear to stand low in the hierarchy of glucoregulatory factors.

Performing resistance exercise before versus after aerobic exercise influences growth hormone secretion in type 1 diabetes

2014 ◽  
Vol 39 (2) ◽  
pp. 262-265 ◽  
Author(s):  
Jane E. Yardley ◽  
Ronald J. Sigal ◽  
Michael C. Riddell ◽  
Bruce A. Perkins ◽  
Glen P. Kenny
Keyword(s):  
Growth Hormone ◽  
Resistance Exercise ◽  
Hepatic Glucose Production ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Glucose Production ◽  
Lipid Mobilization ◽  
Gh Secretion ◽  
Hepatic Glucose

We compared growth hormone (GH) and plasma glucose (PG) levels in type 1 diabetic individuals performing aerobic before resistance exercise (AR) to when resistance exercise was performed first (RA). In AR, GH secretion declined in late exercise while it rose throughout exercise in RA, resulting in higher GH in RA versus AR at exercise completion. Higher GH during RA may support PG by increasing hepatic glucose production and lipid mobilization.

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