UNIPROT:P01275 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UNIPROT:P01275 (glucagon)
26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The serum ketone response to glucagon was measured in 10 patients with IDDM and 37 with NIDDM. In both groups, serum 3-hydroxybutyrate increased significantly after intravenous injection of 1 mg glucagon. The difference between the serum level of 3-hydroxybutyrate at 30 min and basal level [delta 3-OHBA(30')] was 133 +/- 25 mumol/l in the patients with IDDM, 13 +/- 8 mumol/l in those with NIDDM treated by diet alone or with oral hypoglycemic agents and 23 +/- 13 mumol/l in those with NIDDM treated with insulin. The delta 3-OHBA(30') was significantly greater in IDDM patients than in both groups of NIDDM patients (P less than 0.001). The delta 3-OHBA(30') was greater than 87 mumol/l in eighty percent of IDDM patients, but smaller than 87 mumol/l in both groups of NIDDM patients. The delta 3-OHBA(30') was correlated with the difference between the plasma level of C-peptide at 6 min and basal level [delta CPR(6')] (r = -0.540, P less than 0.001). The delta 3-OHBA(30') was not correlated with fasting plasma levels of glucose, fructosamine or hemoglobin A1c. These observations show that measurement of the serum ketone response to glucagon is a useful marker of insulin dependency. In order to determine insulin dependency, the simultaneous measurement of concentrations of ketones and C-peptide is indicated during the glucagon stimulation test.
...
PMID:Serum ketone response to glucagon as a marker of insulin dependency in diabetics. 175 81

We have seen a case of "diabetic non-ketotic hyperosmolar coma" with ketosis. An 84-year-old man was brought into the hospital in a deeply comatous and dehydrated state. The initial blood glucose level was 1252 mg/dl with plasma osmolarity of 435 mOsm/l, but no ketonuria was detected by the nitroprusside method (Ketostix). However, the plasma 3-hydroxybutyrate (3-OHBA) level was 5 mM in a newly developed bedside film test. The serum ketone bodies were later found to be 5.56 and 0.82 mmol/l for 3-OHBA and acetoacetate (AcAc), respectively. A marked increase in glucagon, cortisol and ADH with renal dysfunction (creatinine 5.0 mg/dl) were noted. An abnormal electrocardiogram, occular convergence and chorea like movement disappeared after correction of metabolic disturbances. The moderate level of IRI (14 microU/ml) on admission and a good response to glucagon 2 months after admission also indicate that the present case is a typical hyperosmolar non-ketotic coma. Because of a preferential increase in 3-OHBA, ketonuria seemed to be absent in the regular nitroprusside test. Marked dehydration is thought to cause renal dysfunction, and the increase in ADH may have helped to prevent further aggravation of ketoacidosis. We propose to change the term hyperosmolar non-ketotic coma (HNC) to diabetic hyperosmolar coma (DHC), because sometimes patients with hyperosmolar non-ketotic diabetic coma are ketotic, as seen in the present case. Determination of 3-OHBA or individual ketone bodies in blood is important and essential for the differential diagnosis of diabetic coma. The diagnosis of either ketoacidotic or hyperosmolar coma should be made depending on the major expression of ketoacidosis or hyperglycemic hyperosmolarity.
...
PMID:A case of diabetic non-ketotic hyperosmolar coma with an increase with plasma 3-hydroxybutyrate. 184 65

We examined whether the rise in ketone body concentration around midnight and in the early morning was due to the lack of free insulin (IRI) or excess of insulin counterregulatory hormones such as human growth hormone (hGH), cortisol and glucagon in noninsulin-dependent diabetes mellitus (NIDDM) and insulin-dependent diabetes mellitus (IDDM) patients and whether the monitoring of blood ketone body concentration was clinically useful as an index of metabolic control for deciding to increase or decrease the insulin dose in the treatment of diabetes mellitus. Serum levels of 3-hydroxybutyrate (3-OHBA), acetoacetate (AcAc) and 3-OHBA/AcAc ratio before breakfast were significantly increased in insulin-treated NIDDM patients with well-controlled fasting plasma glucose levels and IDDM patients compared to those in normal subjects. Mirror image diurnal changes were found between serum concentrations of 3-OHBA and serum C-peptide or free IRI in normal subjects and NIDDM patients treated with diet alone or sulfonylurea during the 24-hour daily profiles. However, there were no correlations between 3-OHBA and free IRI in the NIDDM patients treated with insulin and IDDM patients who had a much larger increase in the mean concentration of serum 3-OHBA at 6 a.m. caused by a low concentration of free IRI. Counterregulatory hormones were not increased in IDDM patients compared to normal subjects in the early morning. Cortisol/free IRI and hGH/free IRI molar ratios were significantly increased in NIDDM and IDDM patients compared to normal subjects in the early morning, but glucagon/free IRI molar ratio was not changed between IDDM and normal subjects. In conclusion, the early morning rising of ketone body concentration in insulin-treated diabetic patients, particularly IDDM patients, is due to the absolute lack of free IRI and/or the relative lack of free IRI to the levels of hGH or cortisol, and the monitoring of 3-OHBA is clinically useful as a more sensitive index of metabolic control.
...
PMID:Diurnal variation of blood ketone bodies in insulin-dependent diabetes mellitus and noninsulin-dependent diabetes mellitus patients: the relationship to serum C-peptide immunoreactivity and free insulin. 207 25

1. The present paper reports the effects of dietary modifications on the diurnal pattern of concentrations of certain metabolites and hormones in the peripheral blood of lactating dairy cows. The cows were given fixed rations of hay and high-cereal concentrates in the proportions of 30:70 or 10:90 (w/w). The concentrates were given in either two or six equal meals daily; the hay was given twice daily. 2. Previous reports of the same experiment had shown that milk-fat yield and concentration were reduced by increasing the proportion of concentrates in the diet and increased by more frequent feeding of the concentrates. These changes could be explained in part by changes in rumen volatile fatty acid (VFA) proportions and mean daily concentrations of VFA, particularly propionic acid, and insulin in the peripheral blood, but these factors failed to explain all the increase in milk-fat concentration caused by more frequent feeding. 3. Analysis of blood samples taken at hourly intervals for 24 h at two stages of lactation showed that, in the cows fed six times daily, the concentrations of metabolites and hormones remained relatively constant over the day. In the cows fed twice daily, the concentrations of VFA, 3-hydroxybutyric acid and insulin all increased after both meals whereas the concentrations of glucose and growth hormone tended to fall. The concentration of non-esterified fatty acids tended to increase overnight and fall rapidly after the morning feed. The concentrations of glucagon, thyroxine and prolactin showed no clear pattern in relation to meals. The postprandial responses of propionate, insulin and growth hormone were greater with the higher concentrate diet. 4. The maximum concentration and the diurnal range of concentrations were reduced by more frequent feeding of both diets in the case of propionic acid and of the higher concentrate diet in the case of insulin, but the effects on insulin concentrations of more frequent feeding of the lower concentrate diet were smaller and not significant. The maximum concentration and the diurnal range of concentrations of growth hormone were unaffected by meal frequency. 5. It is concluded that the severity of milk-fat depression in cows fed twice daily is increased by the rapid rise in propionic acid concentration in the peripheral blood after a meal, which in turn increases insulin secretion and may be accompanied by a suppression of growth hormone release. This causes lipogenesis to be diverted towards adipose tissue at the expense of the mammary gland.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:Feeding frequency for lactating cows: diurnal patterns of hormones and metabolites in peripheral blood in relation to milk-fat concentration. 305 1

A high glomerular filtration rate (GFR) is often found early in insulin-dependent diabetes mellitus (IDDM). It has been suggested that high circulating glucose, glucagon, and GH levels could play a role in this increase in GFR. On the other hand, patients with IDDM in poor metabolic control also have high circulating ketone body levels. This study was undertaken to determine whether exogenous D,L-3-hydroxybutyric acid at two infusion rates (40 and 30 mumol kg-1 min-1) for 180 min altered renal plasma flow (RPF), GFR, and the excretion rate of total protein, beta 2-microglobulin, and albumin in 11 normal (N) subjects and 11 IDDM patients in whom euglycemia was achieved and maintained using the insulin-glucose clamp technique. RPF and GFR were measured by a priming-continuous infusion of [125I]hippurate and [51Cr]EDTA, respectively. The 40 mumol kg-1 min-1 D,L-3-hydroxybutyric acid infusion increased RPF and GFR in both N and IDDM subjects. Mean RPF increased from 588 +/- 78 (+/- SD) to 706 +/- 129 mL min-1 1.73 m-2 in N and from 671 +/- 101 to 781 +/- 99 in IDDM. GFR increased from 121 +/- 11 to 151 +/- 15 ml min-1 1.73 m-2 in N and from 136 +/- 11 to 191 +/- 16 in IDDM. The filtration fraction also was significantly higher in IDDM than in N during the D,L-3-hydroxybutyric acid infusion. The 30 mumol kg-1 min-1 D,L-3-hydroxybutyric acid infusion increased RPF and GFR to a somewhat lesser extent in both groups. D,L-3-hydroxybutyric acid infusions increased the tubular reabsorption rate of ketone bodies and sodium. The increase in tubular sodium reabsorption rate was correlated significantly to that in the tubular ketone body reabsorption rate. A significant decrease in urinary pH was found during the D,L-3-hydroxybutyric acid infusion. D,L-3-Hydroxybutyrate sodium salt (30 mumol kg-1 min-1) also was infused in 5 of the 11 diabetic patients. A similar increase in GFR and RPF occurred. Both total protein and beta 2-microglobulin, but not albumin, excretion rates increased during D,L-3-hydroxybutyric acid (40 mumol kg-1 min-1) infusion in N and IDDM subjects. D,L-3-Hydroxybutyric acid infusion did not change plasma glucagon, GH, or renin activity.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:Glomerular filtration rate is increased in man by the infusion of both D,L-3-hydroxybutyric acid and sodium D,L-3-hydroxybutyrate. 329 5

1. The present paper reports the effects on rumen fermentation and plasma metabolites and hormones of giving fixed rations of hay and high-cereal concentrates at different meal frequencies to lactating cows. In Expt 1 the total ration was given in two and twenty-four meals daily and in Expts 2-4 the concentrates were given in two and five or six meals and the hay in two meals daily. The diets contained 600-920 g concentrates/kg. 2. In Expt 1, minimum rumen pH was higher but mean pH was lower when cows were given their ration in twenty-four meals/d rather than two meals/d. 3. In all the experiments, the effects of increased meal frequency on the molar proportions of rumen volatile fatty acids (VFA) were small and not significant, although there was a general tendency for the proportion of acetic acid to increase and that of propionic acid to fall. Increasing the proportion of concentrates in the diet reduced the proportion of acetic acid and increased the proportions of propionic and n-valeric acids. 4. In Expt 3, more frequent feeding was found to reduce the concentration of non-esterified fatty acids in the blood, but changes in other metabolites were small and not significant. Increasing the proportion of concentrates in the diet reduced the concentrations of acetic acid and 3-hydroxybutyric acid and increased the concentrations of propionic acid and glucose. 5. The mean daily concentration of insulin in the blood was reduced by more frequent feeding of the higher-concentrate diet but not of the lower-concentrate diet. The concentration of glucagon also tended to fall with more frequent feeding. Increasing the proportion of concentrates in the diet increased the concentration of insulin. 6. More frequent feeding reduced the depression in milk-fat concentration caused by feeding the low-roughage diets. About three-quarters of the variation in milk-fat concentration could be related to changes in rumen VFA proportions, but the relations for the two meal frequencies had different intercepts although similar curves. The results suggest that milk-fat depression on low-roughage diets with twice-daily feeding was due to a change in rumen VFA proportions accompanied by elevated plasma insulin concentrations. The improvement in milk-fat concentration due to more frequent feeding could be explained partly by the small change in rumen VFA proportions and partly by a reduction in mean plasma insulin concentrations, but these mechanisms did not fully account for the milk-fat responses observed.
...
PMID:Feeding frequency for lactating cows: effects on rumen fermentation and blood metabolites and hormones. 331 80

In primary cultures of rat hepatocytes the glucagon-dependent induction of phosphoenolpyruvate carboxykinase was studied in the presence of putative local hormone and substrate modulators which form clear concentration gradients during liver passage such as adenosine, ketone bodies and ammonia. 1) Adenosine inhibited the induction of phosphoenolpyruvate carboxykinase in a concentration-dependent manner between 50 and 200 microM up to 4 h after glucagon application; AMP had similar, adenine, inosine and guanosine had no effect. Adenosine was almost totally metabolized by the liver cells during the first 4 h of the induction period. The inhibitory action of adenosine was also observed using dibutyryl-cAMP or 8-bromo-cAMP as inducer; it could not be prevented by the adenosine receptor antagonist caffeine nor could it be mimicked by the selective adenosine receptor agonist N6-(phenylisopropyl)adenosine. 2) Acetoacetate suppressed the induction of phosphoenolpyruvate carboxykinase in a concentration-dependent manner between 5 and 20mM during the first 4 h after glucagon addition. beta-Hydroxybutyrate showed no effect. Neither starting with acetoacetate nor with beta-hydroxybutyrate did the cell cultures establish the thermodynamic equilibrium between the two compounds. 3) Ammonia did not affect induction of phosphoenolpyruvate carboxykinase at concentrations up to 2mM. Ammonia was converted to urea within the first 4 h; yet it remained at clearly hyperphysiological concentrations in the medium during that period. It is concluded that the glucagon-dependent induction of phosphoenolpyruvate carboxykinase was modulated by the local hormone adenosine via a mechanism not involving adenylate cyclase and by acetoacetate via an unknown mechanism. The inhibitory action of adenosine may, that of acetoacetate can hardly be physiologically relevant.
...
PMID:Modulation of the glucagon-dependent induction of phosphoenolpyruvate carboxykinase by adenosine, but not ketone bodies or ammonia in rat hepatocyte cultures. Possible significance for the zonal heterogeneity of liver parenchyma. 344 1

1. Adipocytes isolated from epididymal adipose tissue of fed or 24 h-starved rats were incubated with a range of glucagon concentrations in the presence and absence of adenosine deaminase (4 munits/ml). 2. With adenosine deaminase present, the lipolytic response to low concentrations of glucagon (1-6 ng/ml) was considerably enhanced in cells from starved rats. 3. The effect of adenosine deaminase on basal lipolysis was altered after starvation. 4. D-3-Hydroxybutyrate (5 mM) decreased the sensitivity of lipolysis to glucagon. 5. The possible involvement of glucagon-stimulated lipolysis in the regulation of ketogenesis is briefly discussed.
...
PMID:Altered lipolytic response to glucagon and adenosine deaminase in adipocytes from starved rats. 747 32

The bihormonal control by insulin and glucagon of blood ketone body level was studied. Mixed solutions with various molar ratios of glucagon and insulin (G/I) were subcutaneously infused continuously for five days by use of the osmotic minipump in the normal rats. The concentrations of insulin and glucagon solution were set at the high G/I molar ratio, the moderate G/I molar ratio and the low G/I molar ratio. In addition, the moderate G/I molar ratio group was divided into three sub-groups: low glucagon and low insulin, moderate glucagon and moderate insulin, and high glucagon and high insulin. After five days, the rats were decapitated to measure plasma ketone body, free fatty acid (FFA), glucose, insulin and glucagon. The FFA level was not significantly different among three groups. The glucose level was not different between the high and moderate G/I molar ratio groups, and decreased in the low G/I molar ratio group. 3-beta-hydroxybutyrate (3-OHBA) and acetoacetate (AcAc) levels in the high G/I molar ratio group were elevated, and 3-OHBA level in the low G/I molar ratio group was lowered compared to those in the moderate G/I molar ratio group. Among three moderate G/I molar ratio sub-groups, there was no difference in 3-OHBA and AcAc levels. These results demonstrate that plasma ketone body levels are controlled by the plasma G/I molar ratio.
...
PMID:Effect of various glucagon/insulin molar ratios on blood ketone body levels in rats by use of osmotic minipumps. 896 84

Four Dorset wethers were studied in a Latin square design with 72-h periods to determine the metabolic adaptations that occur in support of increased glucose demand in ruminants. Wethers injected at 8-h intervals with excipient or a total of .5, 1.0, or 2.0 g/d of phlorizin excreted an average of 0, 72.7, 97.9, and 98.5 g/d of glucose into the urine, respectively. Both acute (2 to 24 h after the first injection) and chronic (8-h intervals from 8 to 72 h after the first injection) adaptations of plasma variables to phlorizin treatment were assessed. Concentrations of plasma glucose decreased linearly with increasing phlorizin dose during the 1st 24 h of treatment and tended to decrease linearly with phlorizin dose during 8 to 72 h of treatment. Urea N tended to increase linearly during 2 to 24 h and increased linearly during 8 to 72 h. Nonesterified fatty acids increased linearly with phlorizin injection during the entire treatment period. beta-Hydroxybutyrate increased quadratically with phlorizin injection during 2 to 24 h and tended to increase quadratically during 8 to 72 h. The ratio of insulin to glucagon tended to decrease linearly with phlorizin injection during the 1st 24 h but was unaffected from 8 to 72 h. Triiodothyronine, but not thyroxine, tended to decrease linearly with phlorizin injection during 8 to 72 h. Cortisol was not affected by treatment. Digestibilities of energy and N were not affected by treatment. Urinary energy excretion increased with phlorizin injection in proportion to the amounts of glucose excreted into the urine. These data indicate that phlorizin-treated wethers largely adapted to phlorizin treatment by 24 h after the first injection and are a suitable model for further investigations of hepatic adaptation to increased glucose demand in ruminants.
...
PMID:Metabolic adaptation to experimentally increased glucose demand in ruminants. 985 5

1 2 Next >>