Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To test the hypothesis that differing physiological insulin levels can modify the counter-regulatory response to prolonged hypoglycemia, experiments were carried out in 10 healthy male subjects. Insulin was infused subcutaneously for 8 h in two separate randomized protocols, so that steady-state levels of 132 +/- 6 pM (low) and 402 +/- 18 pM (high) were obtained. The fall in plasma glucose was controlled by the glucose-clamp technique. Plasma glucose fell slowly and similarly in both groups, reaching an identical steady-state (final 120 min of each study) level of 3.4 +/- 0.1 mM. Steady-state plasma epinephrine (2.5 +/- 0.4 vs. 1.5 +/- 0.2 nM) and norepinephrine (1.5 +/- 0.2 vs. 1.1 +/- 0.1 nM) were significantly (P < 0.05) greater during high- compared with low-dose insulin infusions. Plasma glucagon was reduced during high compared with low infusions (104 +/- 9 vs. 150 +/- 19 ng/l, P < 0.05). Growth hormone, cortisol, and pancreatic polypeptide increased significantly but were not different during the two insulin infusions. Hepatic glucose production (HGP) was equal during the steady-state period (8.4 +/- 1.0 mumol.kg-1.min-1) of each infusion. Blood lactate levels (1,255 +/- 73 vs. 788 +/- 69 mumol/l, P < 0.02) were increased in high compared with low, but nonesterified fatty acid (205 +/- 43 vs. 579 +/- 65 mumol/l) and 3-hydroxybutyrate (40 +/- 36 vs. 159 +/- 51 mumol/l) were reduced (P < 0.002) during the high-compared with low-dose infusions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of physiological hyperinsulinemia on counterregulatory response to prolonged hypoglycemia in normal humans. 794 20

Growth hormone (GH) hypersecretion has been described in diabetes mellitus and seems to be involved in the pathogenesis of diabetes complications. As pirenzepine (PZ), a cholinergic muscarinic antagonist, is able to inhibit GH hypersecretion in insulin-dependent diabetes mellitus (IDDM), we investigated whether PZ is also able to inhibit spontaneous and stimulated GH-release in non-insulin-dependent diabetes mellitus (NIDDM). Ten non-obese well-controlled patients with NIDDM underwent in random order the following three double-blind one week treatments: placebo (PL), PZ at low dose (PL in the morning plus PZ 50 mg at 22 h) or high dose (PZ 50 mg at 8 h plus 100 mg at 22 h). Pirenzepine administration significantly (p < 0.05) decreased nocturnal GH release after both low and high dose (AUC, PL vs PZ: 107.3 +/- 26.5 vs 48.3 +/- 10.5 and 57.6 +/- 9.6 micrograms/L/h, respectively). The GH response to arginine infusion was significantly inhibited by PZ at high dose (AUC, 147.1 +/- 48.8 vs 444.7 +/- 194.3 micrograms/L/h, p < 0.01), but not at low dose. Glucose, insulin, glucagon and somatostatin responses to arginine infusion were not changed by pirenzepine treatment. In conclusion, the muscarinic blockade by PZ is able to inhibit the spontaneous and stimulated GH secretion also in NIDDM without affecting insulin secretion.
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PMID:Pirenzepine decreases basal and stimulated GH secretion in patients with type 2 (non-insulin-dependent) diabetes mellitus. 800 63

Recombinant human insulin-like growth factor-1 (rhIGF-1) lowers blood glucose in humans but its effect on counterregulatory responses has not been established. We therefore compared infusions of rhIGF-1 (0.7 micrograms/kg per min) and insulin (0.8 mU/kg.min) for 120 min in 10 healthy volunteers (glucose allowed to fall freely). With both, glucose fell rapidly because of stimulation of glucose uptake and suppression of hepatic glucose production. Despite similar plasma glucose nadirs (2.6 +/- 0.1 vs. 2.7 +/- 0.1 mM), the glucagon response was absent (P < 0.005), growth hormone release was attenuated (P < 0.03), and norepinephrine levels were increased (P < 0.05) by rhIGF-1 compared with insulin. Absent glucagon responses were associated with a blunting of the rebound increase in glucose production (P < 0.05 vs. insulin). After stopping the infusions, glucose recovery was delayed with rhIGF-1 (P < 0.001 vs. insulin). To further evaluate the effects of rhIGF-1 during a standard hypoglycemic stimulus, eight additional healthy subjects received rhIGF-1 or insulin while glucose was clamped at 2.8 mM. Again the rise in glucagon during insulin-induced hypoglycemia was totally abolished by rhIGF-1. Growth hormone responses were delayed, whereas increases in norepinephrine, heart rate, and symptomatic awareness of hypoglycemia were greater with rhIGF-1 compared with insulin (P < 0.05). It was concluded that rhIGF-1 suppression of glucagon release during hypoglycemia impairs glucose recovery. Paradoxically, awareness of hypoglycemia is enhanced with rhIGF-1 in part due to stimulation of the sympathetic activity.
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PMID:Effect of insulin-like growth factor-1 on the responses to and recognition of hypoglycemia in humans. A comparison with insulin. 842 14

Glucose counterregulation, the physiological mechanisms that normally very effectively prevent or correct hypoglycemia, involves both dissipation of insulin and activation of glucose counterregulatory (glucose-raising) systems. Glucagon and epinephrine stand high in the hierarchy of redundant counterregulatory factors. Hypoglycemia develops or progresses when both glucagon and epinephrine are deficient and insulin is present despite the actions of other glucose-counterregulatory factors. Growth hormone (like cortisol) is demonstrably involved in defense against prolonged (as opposed to short-term) hypoglycemia, but it is not critical to recovery from even prolonged hypoglycemia or to the prevention of hypoglycemia after an overnight fast. Thus, growth hormone, like cortisol, stands lower in the hierarchy of the redundant glucose-counterregulatory factors.
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PMID:Role of growth hormone in glucose counterregulation. 895 Jun 20

While all the hormones described have regulatory effects on the rates of protein synthesis and breakdown there is a complex interaction between them in this control process. Insulin, GH and IGF-I play a dominant role in the day-to-day regulation of protein metabolism. In humans insulin appears to act primarily to inhibit proteolysis while GH stimulates protein synthesis. In the post-absorptive state IGF-I has acute insulin-like effects on proteolysis but in the fed state, or when substrate is provided for protein synthesis in the form of an amino acid infusion, IGF-I has been shown to stimulate protein synthesis. Growth hormone and testosterone have an important role during growth but continue to be required to maintain body protein during adulthood. Thyroid hormones are also required for normal growth and development. The hormones glucagon, glucocorticoids and adrenaline are all increased in catabolic states and may work in concert to increase protein breakdown in muscle tissue and to increase amino acid uptake in liver for gluconeogenesis. While increased glucocorticoids result in reduced muscle mass the effects of glucagon may be predominantly in the liver resulting in increased uptake of amino acids. In contrast to the catabolic effect of adrenaline on glucose and lipid metabolism, studies to date suggest that adrenaline may have an anti-catabolic effect on protein metabolism. Despite this adrenaline increases the production of the gluconeogenic amino acid alanine by muscle and its uptake by the splanchnic bed. There is considerable interest in the use of anabolic hormones, either alone or in combination, in the treatment of catabolic states. GH combined with insulin has been shown to improve whole-body and skeletal muscle kinetics while GH combined with IGF-I has a greater positive effect on protein metabolism in catabolic states than either hormone alone. If catabolic states are to be treated successfully a greater understanding of the role of the catabolic hormones in these states and the possible treatment of these states with anabolic hormones is required.
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PMID:The hormonal control of protein metabolism. 902 51

Hepatic glucose production increases during exercise as a sum of liver glycogenolysis and gluconeogenesis. Whereas the former dominates during intense exercise, the latter contributes substantially with prolonged exercise and the concomitant decline in liver glycogen stores and with increased gluconeogenic precursor supply. Afferent neural feedback signals from contracting muscle and feedback signals mediated via the blood stream, can stimulate glucose production to maintain euglycemia. A rise in blood glucose directly inhibits hepatic glucose production, whereas a decline in blood glucose enhances liver glucose production via release of glucoregulatory hormones. In addition to this, central mechanisms coupled to the degree of motor center activity can be responsible for part of the increase in glucose mobilization, especially during intense exercise where hepatic glucose release exceeds peripheral glucose uptake and plasma glucose rises. A decline in plasma insulin is important for the rise in glucose production during exercise in a variety of species, whereas an increase in plasma glucagon is probably more important in other species than man, where glucagon plays a role only in prolonged exercise. Sympathetic nervous activity to the liver and circulating norepinephrine has been demonstrated to be without any role in glucose production, whereas epinephrine has a minor stimulating effect on hepatic glucose mobilization during intense exercise. Growth hormone and cortisol contribute only minimally to the exercise induced rise in liver glucose output.
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PMID:Hepatic glucose production during exercise. 978 19

Growth hormone (GH) has insulin-antagonistic effects, and GH secretion is augmented during fasting and hypoglycemia. In the present study, 10 patients aged 21 to 28 years with childhood-onset GH deficiency (GHD) were studied during a 24-hour fast and a hypoglycemic glucose clamp before and after 9 months of GH replacement. During the 24-hour fast, blood glucose, serum insulin, and serum free fatty acid (FFA) levels were measured. In the hypoglycemic clamp, the counterregulatory hormones (plasma catecholamines, serum glucagon, and serum cortisol), serum insulin-like growth factor (IGF) binding protein-1 (IGFBP-1), serum FFA, and glucose uptake were measured. The GH dose was adjusted to the response of serum IGF-I, and the median GH dose was 0.14 IU/kg/wk (range, 0.08 to 0.19). At the end of the study, serum IGF-I levels were normalized in all but one patient, in whom serum IGF-I was above the normal range. Nine months of GH treatment did not cause any significant changes in the blood glucose level, insulin to glucose ratio, or serum FFA level during the 24-hour fast, and none of the patients experienced hypoglycemia either before or after GH treatment. However, GH therapy resulted in increased insulin resistance during hypoglycemia, without changes in the counterregulatory hormonal responses, serum IGFBP-1, or serum FFA.
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PMID:Individualized low-dose growth hormone (GH) treatment in GH-deficient adults with childhood-onset disease: metabolic effects during fasting and hypoglycemia. 1045 65

To establish reference intervals for the pancreatic beta-cell response and the counterregulatory hormone response to prolonged fasting, we studied 33 healthy subjects (16 males, 17 females) during a 72-h fast. Glucose, insulin, C-peptide, and proinsulin levels decreased (P < 0.001), and the levels of counterregulatory factors increased during the fast [P < 0.05; glucagon and free fatty acids (FFA) with a linear increase and epinephrine, norepinephrine, and cortisol with a clear underlying circadian rhythm]. Growth hormone secretion increased from the first to third day of fasting (P < 0.05) but actually decreased from the second to third day of fasting (P = 0.03). Males had higher glucose and glucagon levels and lower FFA levels during the fast (P < 0.05), whereas no effect of gender on beta-cell polypeptides was observed. A high body mass index resulted in higher insulin and C-peptide levels during the fast (P < 0.05). In conclusion, we have provided reference intervals for glucoregulatory factors during a 72-h fast. We observed a diminished beta-cell response concomitant with an increased secretion of counterregulatory hormones. These results should be of clinical and scientific value in the investigation of hypoglycemic disorders.
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PMID:Reference intervals for glucose, beta-cell polypeptides, and counterregulatory factors during prolonged fasting. 1112 Jun 58

We tested the hypothesis that increased endogenous cortisol secretion reduces autonomic neuroendocrine and neurogenic symptom responses to subsequent hypoglycemia. Twelve healthy young adults were studied on two separate occasions, once after infusions of a pharmacological dose of alpha-(1-24)-ACTH (100 microg/h) from 0930 to 1200 and 1330 to 1600, which raised plasma cortisol levels to approximately 45 microg/dl on day 1, and once after saline infusions on day 1. Hyperinsulinemic (2.0 mU x kg(-1) x min(-1)) stepped hypoglycemic clamps (90, 75, 65, 55, and 45 mg/dl glucose steps) were performed on the morning of day 2 on both occasions. These markedly elevated antecedent endogenous cortisol levels reduced the adrenomedullary (P = 0.004, final plasma epinephrine levels of 489 +/-64 vs. 816 +/-113 pg/ml), sympathetic neural (P = 0.0022, final plasma norepinephrine levels of 244 +/-15 vs. 342 +/-22 pg/ml), parasympathetic neural (P = 0.0434, final plasma pancreatic polypeptide levels of 312 +/- 37 vs. 424 +/- 56 pg/ml), and neurogenic (autonomic) symptom (P = 0.0097, final symptom score of 7.1 +/-1.5 vs. 10.6 +/- 1.6) responses to subsequent hypoglycemia. Growth hormone, but not glucagon or cortisol, responses were also reduced. The findings that increased endogenous cortisol secretion reduces autonomic neuroendocrine and neurogenic symptom responses to subsequent hypoglycemia are potentially relevant to cortisol mediation of hypoglycemia-associated autonomic failure, and thus a vicious cycle of recurrent iatrogenic hypoglycemia, in people with diabetes mellitus.
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PMID:Elevated endogenous cortisol reduces autonomic neuroendocrine and symptom responses to subsequent hypoglycemia. 1188 96

Short-bowel syndrome refers to malabsorption, diarrhea, and weight loss following an extensive resection of small bowel. A main consequence is malabsorption of macro- and micronutrients. Nutritional outcome after intestinal resection depends on the extent and location of resection, presence of ileocecal valve and a colon, functional status of the residual intestine, and adaptation. Intraluminal nutrients and trophic factors are critical for intestinal adaptation. The dietary management is focused on the enhancement of intestinal adaptation and optimal caloric intake. Patients with short-bowel syndrome require an individualized diet, and some may require total parenteral nutrition indefinitely. Growth hormone, glutamine, and GLP-2 are reviewed with emphasis on their current use in clinical practice. The nutritional aspect of short-bowel syndrome is complex, with the ultimate goal of weaning the patients from parenteral nutrition. Intestinal transplant is a treatment option for select patients.
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PMID:Nutritional management of short bowel syndrome. 1223 Mar 19


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