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)

The effects of nonselective beta-blockade (propranolol) and beta-1-selective blockade (atenolol) on glucose metabolism during insulin-induced hypoglycemia were studied in eight normal subjects during constant infusion of 3-[3H]glucose. Propranolol and to a lesser extent atenolol prolonged the hypoglycemic response to insulin. After maximal hypoglycemia a significant increase in glucose uptake rate was seen after propranolol and a corresponding trend was found in the atenolol experiments. The two beta-blockers did not influence glucose production rate after insulin administration. FFA concentration declined rapidly after insulin. Propranolol delayed the subsequent normalization of FFA whereas atenolol had no significant effect. Propranolol increased epinephrine and GH responses to hypoglycemia, whereas atenolol had no effect. Neither of the two beta-blockers influenced the concentrations of glucagon, norepinephrine, and PRL. It is concluded that nonselective beta-blockade prolongs the hypoglycemic response to insulin through an increased tissue uptake of glucose which is not counteracted by an increased glucose production. It is suggested that nonselective beta-blockade increases muscle glucose uptake by lowering FFA concentrations. beta-Blocker inhibition of the antiinsulin effect of epinephrine on glucose uptake in muscle can, however, not be excluded.
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PMID:Effects of nonselective and beta-1-selective blockade on glucose metabolism and hormone responses during insulin-induced hypoglycemia in normal man. 633 40

The metabolic response to exercise in insulin-dependent diabetic (IDD) man was assessed during continuous insulin infusion using the subcutaneous (CSII), intravenous (CIVII), and intraperitoneal (CIPII) routes. During the basal period, plasma glucose levels were higher with CIPII (153 +/- 17 mg/dl) than with CSII (117 +/- 13 mg/dl) or CIVII (118 +/- 17 mg/dl). Basal free insulin concentrations were similar for CSII (12.3 +/- 10 microU/ml) and CIVII (12.4 +/- 1.4 MicroU/ml) but lower in CIPII (8.5 +/- 1.0 microU/ml, P less than 0.05). Exercise on a stationary bicycle at 75 W for 60 min produced a decline of plasma glucose in each protocol that was significantly only during CIVII (55 +/- 11 mg/dl, P less than 0.01). Insulin levels remained unchanged throughout the study period in all protocols. In normals, insulin values decreased during exercise and remained below basal levels through the recovery period (P less than 0.05), while plasma glucose remained unchanged. Plasma glucagon and epinephrine levels were similar in all protocols and remained unchanged with exercise, while plasma norepinephrine tended to be higher than normal in all diabetic subjects. Significant differences between normal and diabetic subjects (P less than 0.05) were observed for blood ketone bodies, while blood lactate, glycerol, and plasma FFA were similar. Normalization of intermediary metabolites occurred only with CIVII. Continuous insulin infusion provides near-normal glycemic and metabolic control before, during and following exercise in IDD man. However, to produce normal blood concentrations of intermediary metabolites during exercise, the insulin infusion rate may be excessive in terms of its hypoglycemic effect. CSII appears to be a safe, accessible, and adequate method for treating diabetic man during exercise.
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PMID:Exercise in insulin-dependent diabetes mellitus: the effect of continuous insulin infusion using the subcutaneous, intravenous, and intraperitoneal sites. 634 16

Two chemically unrelated inhibitors of lipolysis were used in order to differentiate between the effect of FFA depression and a possible FFA-unrelated drug effect, respectively, on the plasma concentrations of GH, cortisol, and glucagon. Saline infusion served as a control experiment. In eight healthy male volunteers, a similar FFA depression by either iv infusion of nicotinic acid (3-pyridine-carboxylic acid, NA) or oral intake of an adenosine derivative, N(6)-allyl-N(6)-cyclohexyl-adenosine (AD-D), was followed by a significant GH increase (to 22.1 +/- 6.2 and 9.6 +/- 2.9 ng/ml at 240 and 270 min, respectively). Due to the large scatter of the GH concentrations during NA infusion, these responses were not significantly different. No GH increase occurred when the FFA depression was prevented by addition of a lipid infusion. In contrast, plasma cortisol and glucagon both increased significantly (by 107.4 micrograms/liter at 270 min and by 48.4 pg/ml at 60 min, respectively) during NA- but not during AD-D-induced FFA depression. Addition of the lipid infusion abolished the cortisol increase during NA infusion but had no influence on basal cortisol concentrations during AD-D intake. It lowered glucagon to values slightly below basal concentrations when added to the NA infusion and more markedly during AD-D administration. The results provide evidence that 1) depression of plasma FFA per se stimulates the secretion of GH, and 2) the increase of cortisol and glucagon during NA infusion is probably unrelated to the FFA depression. Hence, the stimulatory effect of FFA lack on glucagon secretion needs to be reconsidered.
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PMID:Growth hormone, cortisol, and glucagon concentrations during plasma free fatty acid depression: different effects of nicotinic acid and an adenosine derivative (BM 11.189). 634 70

The influence of ketone body infusion on the serum GH and glucagon response to FFA depression and insulin hypoglycemia was investigated in 10 healthy men. Intravenous infusion of nicotinic acid induced suppression of both FFA and ketone bodies. This was accompanied by a delayed GH increase to 21.1 +/- 6.9 ng/ml (at 300 min). During an additional beta-hydroxybutyrate (OHB) infusion, FFA remained depressed, but ketone bodies were elevated, and the GH response was abolished (maximum 5.6 +/- 1.6 ng/ml). During infusion of OHB alone, FFA were suppressed. GH increased significantly, although less markedly than during suppression of both FFA and ketone bodies (to 9.3 +/- 3.1 ng/ml at 270 min). No GH rise occurred when both FFA and ketone bodies were kept elevated by the addition of a lipid infusion. The GH rise in response to insulin hypoglycemia was not changed by an OHB infusion (43.2 +/- 4.6 vs. 48.0 +/- 7.3 ng/ml). However, OHB increased the net GH output by significantly delaying the return to basal concentrations in the presence of a reduced FFA rebound. An effect of OHB infusion on the plasma glucagon concentration during all experiments was small, and its physiological significance is doubtful. These results confirm that FFA depression induces delayed GH secretion. They suggest that this is not wholly dependent on concomitant depression of ketone bodies. On the other hand, when ketone bodies are elevated, the GH response to FFA depression is diminished or absent. The net GH response to changes in lipid substrates probably depends on the concentration of both FFA and ketone bodies.
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PMID:Influence of ketone body infusion on plasma growth hormone and glucagon in man. 634 66

Acute infections are accompanied by tissue insulin resistance, as manifested by worsening of metabolic control in diabetic patients and decreased glucose tolerance in non-diabetic subjects. To clarify the potential role of altered insulin receptor status in this phenomenon, we studied [125I]insulin binding to monocytes in 7 otherwise healthy subjects during acute bacterial and viral infections of moderate severity. The values were compared to those obtained after convalescence (five patients) and those of 24 normal subjects. Insulin binding during infection, at a time when insulin resistance was demonstrable, was indistinguishable from convalescent or normal values. Plasma glucose and insulin levels, the insulin to glucose ratio, as well as plasma GH, cortisol, and FFA were significantly elevated during infection, while plasma glucagon, epinephrine, and norepinephrine levels were normal. We conclude that insofar as monocyte receptors are representative of other tissues, insulin resistance in infection is mediated at the postreceptor level.
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PMID:Insulin receptors in acute infection: a study of factors conferring insulin resistance. 636 46

Epinephrine (10 micrograms/kg body weight) s.c., glucagon (1 microgram/kg body weight) i.v. and glucose (0.5 g/kg body weight) i.v. were injected in groups of ketosis-prone young diabetics, ketosis-resistant young diabetics, maturity-onset diabetics, young and mature controls, each group comprising 8 subjects. Samples were drawn at timed intervals and analyzed for glucose, FFA, acetone, citrate and plasma free insulin. FFA and glycerol release by the adipose tissue in vitro was studied in 6 of each of the following groups: young diabetics and young controls in the presence of norepinephrine, anti-insulin serum or both. Failure of the adipose tissue of ketosis-resistant young diabetics to respond to lipolytic and ketogenic hormones has been suggested by others as the basis for the clinically observed resistance to ketoacidosis. The present data do not confirm any failure of the liver or adipose tissue to respond to glucagon, epinephrine or norepinephrine in these diabetics. The ketosis-resistant young diabetics have some endogenous insulin secretory capacity still preserved as evident from their basal and post-glucose free insulin levels and effects of anti-insulin serum on in vitro lipolysis by their adipose tissues. The available endogenous insulin though adequate in preventing excessive lipolysis and ketogenesis, appears insufficient to check hyperglycemia.
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PMID:Biochemical characterization of ketosis-resistant young diabetics of northern India. In vivo effects of i.v. glucose, s.c. epinephrine and i.v. glucagon and in vitro effects of anti-insulin serum on adipose tissue lipolysis. 643 9

A 31-year old female presented with recurrent episodes of post-prandial hypoglycaemic symptoms. Basal serum levels of ACTH, cortisol, GH, insulin and glucagon were normal. An adrenaline test demonstrated a normal peripheral response. An exercise test failed to produce ACTH, cortisol or FFA responses. Insulin (0.1 u/kg)-induced-hypoglycaemia failed to elevate serum ACTH, cortisol or GH. Metyrapone and ACTH tests were normal, demonstrating adequate hypophyseal and adrenal function. These findings suggested that the patient suffered from hypothalamic dysfunction. Bromocriptine (Parlodel, 7.5 mg/d for 5 weeks) resulted in an improved general condition, accompanied by a decrease in sugar consumption. Following treatment, FFA, ACTH and cortisol responses to exercise test were normal, as were ACTH, cortisol and GH responses to insulin-induced hypoglycaemia. It is concluded that bromocriptine may be useful in the treatment of post-prandial hypoglycaemic symptoms associated with hypothalamic dysfunction.
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PMID:Correction by bromocriptine of hypothalamic dysfunction and post-prandial hypoglycaemic symptoms in a 31-year-old woman. 662

Nine insulin-dependent diabetics and six healthy controls were studied at rest, during, and after 60 min of bicycle exercise at a work load corresponding to 45% of their maximal oxygen intake. The catheter technique was employed to determine splanchnic and leg exchange of metabolites. FFA turnover and regional exchange was evaluated using [14C]oleate infusion. Basal glucose (13.8 +/- 1.1 mmol/l), ketone body (1.12 +/- 0.12 mmol/l), and FFA (967 +/- 110 mumol/l) concentrations were elevated in the diabetics in comparison with controls. In the resting state, splanchnic ketone acid production in the diabetics was 6-10-fold greater than in controls. Uptake of oleic acid by the splanchnic bed was increased 2-3-fold, and the proportion of splanchnic FFA uptake converted to ketones (61%) was threefold greater than in controls. In contrast, splanchnic fractional extraction of oleic acid was identical in diabetics and controls. A direct relationship was observed between splanchnic uptake and splanchnic inflow (plasma concentration X hepatic plasma flow) of oleic acid that could be described by the same regression line in the diabetic and control groups. During exercise, splanchnic ketone production rose in both groups. In the control group the increase in ketogenesis was associated with a rise in splanchnic inflow and in uptake of oleic acid, a rise in splanchnic fractional extraction of oleate, and an increase in the proportion of splanchnic FFA uptake converted to ketone acids from 20-40%. In the diabetic group, the increase in ketogenesis occurred in the absence of a rise in splanchnic inflow or uptake of oleic acid, but was associated with an increase in splanchnic fractional extraction of oleic acid and a marked increase in hepatic conversion of FFA to ketones, so that the entire uptake of FFA was accountable as ketone acid output. Splanchnic uptake of oleic acid correlated directly with splanchnic oleic acid inflow in both groups, but the slope of the regression line was steeper than in the resting state. Plasma glucagon levels were higher in the diabetic group at rest and during exercise, while plasma norepinephrine showed a twofold greater increment in response to exercise in the diabetic group (to 1,400-1,500 pg/ml). A net uptake of ketone acids by the leg was observed during exercise but could account for less than 5% of leg oxidative metabolism in the diabetics and less than 1% in controls. Despite the increase in ketogenesis during exercise, a rise in arterial ketone acid levels was not observed in the diabetics until postexercise recovery, during which sustained increments to values of 1.8-1.9 mmol/l and sustained increases in splanchnic ketone production were observed at 30-60 min. The largest increment in blood ketone acids and in splanchnic ketone production above values observed in controls thus occurred in the diabetics after 60 min of recovery from exercise. We concluded that: (a) In the resting state, increased ketogenesis in the diabetic is a consequence of augmented splanchnic inflow of FFA and increased intrahepatic conversion of FFA to ketones, but does not depend on augmented fractional extraction of circulating FFA by the splanchnic bed. (b) Exercise-induced increases in ketogenesis in normal subjects are due to augmented splanchnic inflow and fractional extraction of FFA as well as increased intrahepatic conversion of FFA to ketones. (c) When exercise and diabetes are combined, ketogenesis increases further despite the absence of a rise in splanchnic inflow of FFA. An increase in splanchnic fractional extraction of FFA and a marked increase intrahepatic conversion of FFA to ketones accounts for the exaggerated ketogenic response to exercise in the diabetic. (d) Elevated levels of plasma glucagon and/or norepinephrine may account for the increased hepatic ketogenic response to exercise in the diabetic. (e) Ketone utilization by muscle increases during exercise but constitutes a quantitatively minor oxidative fuel for muscle even in the diabetic. (f) The accelerated ketogenesis during exercise in the diabetic continues unabated during the recovery period, resulting in an exaggerated postexercise ketosis.
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PMID:Turnover and splanchnic metabolism of free fatty acids and ketones in insulin-dependent diabetics at rest and in response to exercise. 671 41

We infused physiological doses of epinephrine (1.2 microgram/m2 X min) into six healthy obese subjects in the postabsorptive state and after 3-4 days of starvation. During starvation, a reduction in hepatic glycogen stores was demonstrated by the absence of a rise in plasma glucose and glucose production (using [3-3H]glucose) in response to glucagon infusion. The increases in plasma epinephrine and glucose during the epinephrine infusion were comparable before and after starvation. Most importantly, the increase in endogenous glucose production produced by epinephrine was virtually unaffected, i.e. the initial rise in glucose production (59% vs. 49%), the incremental area under the curve (2.6 vs. 3.1 g/m2), and the spike-decline pattern of the response were no different before and after starvation, respectively. Similarly, epinephrine-induced elevations in gluconeogenic precursors (lactate and alanine) were not altered by starvation. However, starvation accentuated the rise in FFA by 200%. We conclude that starvation does not diminish the rise in endogenous glucose production in response to stress-like elevations of epinephrine. This occurs even though the liver fails to respond to high physiological doses of glucagon, possibly because epinephrine enhances the mobilization of gluconeogenic precursors and FFA. These data suggest that epinephrine is a potent stimulator of gluconeogenesis and may be more effective than glucagon in accelerating glucose production in patients with depleted glycogen stores.
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PMID:Epinephrine-stimulated glucose production is not diminished by starvation: evidence for an effect on gluconeogenesis. 672 6

The present study was conducted in 12 healthy volunteers to determine the effect of porcine insulin (0.15 U/kg i.v.) on a number of different metabolic and hormonal parameters measured simultaneously. The nadir of blood glucose (19.0 +/- 2.7 ng/100 ml) is detected 30 min following insulin application, paralleled by suppressed levels of FFA and beta-hydroxybutyrate. The lowest level of potassium (3.39 +/- 0.09 mval/l) is observed 45 min following insulin application. The hormones of counterregulation show an uniform pattern of response. Peak levels of norepinephrine (228.9 +/- 36.0 ng/l) and epinephrine (720.6 +/- 125.6 ng/l) are observed at 30 and 45 min, those of cAMP (33.4 +/- 2.5 pmol/ml), glucagon (0.209 +/- 0.024 ng/ml), ACTH (166.0 +/- 40.1 ng/ml), and prolactin (28.1 +/- 7.8 ng/ml) at 45 min and finally those of cortisol (26.1 +/- 3.3 micrograms/100 ml) and growth hormone (21.6 +/- 3.1 ng/ml) at 60 min following insulin injection. As the blood glucose level is already rising after 30 min it is concluded that the catecholamines and glucagon play a major part in the restitution of normal blood glucose levels. At the end of the test, blood glucose and hormone levels have almost normalized, but FFA and beta-hydroxybutyrate levels are doubled and almost triplicated as compared to the starting point levels.
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PMID:Hormonal and metabolic parameters following insulin-induced hypoglycemia. 675 13


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