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)

Intensive insulin treatment during diabetic pregnancy is complicated by maternal hypoglycemia. To investigate whether pregnancy may contribute as an independent hypoglycemia risk factor, awake pregnant rats that were near term underwent stepped insulin hypoglycemic (3.4 and 2.3 mM) clamp studies in the fasted and nonfasted states. In the fasted state, the glucagon response to hypoglycemia was completely suppressed in the pregnant rats (P < 0.01). Epinephrine, but not norepinephrine, was also diminished by approximately 70-75% at both hypoglycemic steps, and more exogenous glucose was needed to maintain hypoglycemia during pregnancy. To avoid the potential confounding effect of increased ketone levels (beta-hydroxybutyrate was approximately 170% higher in the pregnant rats), experiments were repeated in the nonfasting state when ketosis was eliminated in both groups. The nonfasted pregnant rats continued to show near complete suppression of the glucagon response, even at glucose levels of 2.3 mM. In contrast, a brisk response occurred in nonpregnant controls when glucose fell to 3.4 mM. Although epinephrine levels in the pregnant rats were also markedly suppressed during the milder hypoglycemic stimulus, they approached values seen in nonpregnant controls when glucose was lowered further to 2.3 mM. We concluded that in the rat, pregnancy markedly suppresses glucagon responses to hypoglycemia. The release of epinephrine, but not norepinephrine, is also blunted, especially during mild hypoglycemia. These findings suggest that pregnancy may impair glucose counterregulation by inhibiting glucagon and epinephrine release during hypoglycemia.
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PMID:Inhibitory effect of pregnancy on counterregulatory hormone responses to hypoglycemia in awake rat. 837 83

A glucose tolerance test was carried out on 8 ketotic dairy cows and 5 healthy dairy cows after injection of 500 ml of 50% glucose solution into the jugular vein. The blood insulin concentration increased from 6.3 microU/ml before glucose injection to 62.5 microU/ml after injection in the healthy group and from 3.0 to 22.9 microU/ml in the ketotic group. Insulin concentration before glucose injection was lower, and its increase after glucose injection was smaller, in the ketotic group. Five hundred milliliters of 50% glucose solution were administered to 15 ketotic cows by intravenous infusion once daily from d 1 to 6, and 200 U of insulin were injected subcutaneously in 8 of these cows from d 2 to 6. In the group administered insulin with glucose, the blood glucose concentration, insulin concentration, and insulin to glucagon ratio (50.5 mg/dl, 6.2 microU/ml, and .09, respectively) on d 6 were significantly higher than those for cows administered glucose only (36.3 mg/dl, 3.0 microU/ml, and .04, respectively). Also, the blood ketone bodies and free fatty acid concentrations on d 6 were significantly lower in the group receiving glucose plus insulin (22.1 microU/ml and .79 meq/L, respectively) than in the group receiving glucose alone (63.8 microU/ml and .98 meq/L, respectively). Thus, the simultaneous use of glucose and insulin is considered to be useful for the treatment of ketosis in dairy cows.
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PMID:Therapeutic effects of simultaneous use of glucose and insulin in ketotic dairy cows. 843 69

To determine the etiology of euglycemic ketoacidosis, the effect of a 32-h fast on the rate of metabolic deterioration was examined in a group of 10 healthy subjects with type I diabetes mellitus. Patients were studied during 5 h of insulin withdrawal after 8 h (postprandial) and 32 h (fasted) of food deprivation. Study parameters included substrate levels, electrolytes, counterregulatory hormone levels, and rates of glucose and glycerol turnover. In the fasted state, mean peak plasma glucose concentrations were significantly lower than those in the 8-h postprandial state (13.3 +/- 1.6 vs. 17.4 +/- 1.4 mmol/L, respectively; P < 0.05), and mean rates of glucose production were also significantly lower at all time points in the fasting state. The rate of development of ketosis was significantly more rapid during insulin deficiency after a fast (8.82 +/- 0.63 vs. 6.23 +/- 0.30 micro/L.min; P < 0.05), while plasma nonesterified fatty acids and glycerol turnover showed a biphasic response to insulin withdrawal, which was also more robust after a fast. Metabolic acidosis, as reflected in the rate of decrease in serum bicarbonate concentration, was more severe after 32 h of fasting than in the postprandial state (mean nadir, 15.4 +/- 0.9 vs. 18.6 +/- 0.5 mmol/L; P < 0.001). In contrast to values in the postprandial state, serum glucagon levels rose during insulin withdrawal in the fasting state, and plasma norepinephrine levels also correlated positively with the ongoing metabolic decompensation. Other counterregulatory hormones did not differ significantly in the fasted vs. postprandial states in these short term metabolic studies. We conclude that a fast of moderate duration, such as might be expected to occur during the development of diabetic ketoacidosis, predisposes patients with type I diabetes to euglycemic ketoacidosis during periods of insulin deficiency. Furthermore, decreased rates of hepatic glucose production are responsible for the lower plasma glucose values observed during a fast. The development of ketosis continued progressively in both conditions, but the rate of rise of plasma ketones was increased in the fasted state. This accelerated development of ketosis may be attributable to the effects of elevated levels of glucagon and/or catecholamines on lipolysis.
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PMID:Short-term fasting is a mechanism for the development of euglycemic ketoacidosis during periods of insulin deficiency. 849 10

A majority of patients with fibrocalculous pancreatic diabetes (FCPD) do not become ketotic even in adverse conditions. It is not clear whether this ketosis resistance is due to reduced fatty acid release from adipose tissue or to impaired hepatic ketogenesis. We tested hepatic ketogenesis in FCPD patients using a ketogenic challenge of oral medium-chain triglycerides (MCTs) and compared it with that in matched insulin-dependent diabetes mellitus (IDDM) patients and healthy controls. After oral MCTs, FCPD patients showed only a mild increase in blood 3-hydroxybutyrate (3-HB) concentrations (median: fasting, 0.13 mmol/L; peak, 0.52) compared with IDDM patients (fasting, 0.44; peak, 3.39) and controls (fasting, 0.04; peak, 0.75). Plasma nonesterified fatty acid (NEFA) concentrations were comparable in the two diabetic groups (FCPD: fasting, 0.50 mmol/L; peak, 0.79; IDDM: fasting, 0.91; peak, 1.04). Plasma C-peptide concentrations were low and comparable in the two diabetic groups. Plasma glucagon concentrations were higher in IDDM patients in the fasting state, but declined to levels comparable to those in FCPD patients after oral MCTs. Plasma carnitine concentrations were comparable in the two groups of patients. It is concluded that the failure to stimulate ketogenesis under these conditions could be partly due to inhibition of a step beyond fatty acid entry into the mitochondria.
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PMID:Ketosis resistance in fibrocalculous pancreatic diabetes: II. Hepatic ketogenesis after oral medium-chain triglycerides. 900 60

Increased lipolysis, low insulin/glucagon ratios and malonyl-CoA concentrations are prerequisites for ketogenesis. From an aetiological viewpoint, there are two quite different types of metabolic disorders in which ketosis can occur, the hypoglycaemic-hypoinsulinaemic and the hyperglycaemic-hyperinsulinaemic type. The former, Type I, generally occurs 3-6 weeks after calving in cows whose milk secretion is so extensive that the demand for glucose exceeds the capacity for glucose production. To protect the body from hazardous protein degradation by a high rate of gluconeogenesis, this process is inhibited and the increased energy requirements are met by the elevated utilization of ketone bodies. In this strong catabolic metabolic state the plasma levels of glucose and insulin are very low, the levels of ketone bodies are high and there are small risks for fat accumulation in the liver cells. The hyperglycaemic, hyperinsulinaemic form, Type II, generally occurs earlier in lactation. An important aetiologic factor is overfeeding in the dry period, which can lead to disturbances in the hormonal adaptation of metabolism at calving with increased plasma levels of insulin and glucose and often out not always also with hyperketonaemia. If combined with stress, there may be increased lipolysis in adipose tissues, lipid synthesis and accumulation in the liver, i.e. the development of fatty liver. This hyperglycaemic form of disturbance has many similarities with the initial stage of non-insulin-dependent (Type II) diabetes in humans. It has been shown that ketone bodies inhibit protein degradation and thereby gluconeogenesis and also are able to spare glucose by inhibiting glucose utilization. They also can inhibit lipolysis and function as a regulatory safety system, replacing insulin, in situations when the activity of this hormone is low, as in Type I ketosis. Ketone bodies thus have important functions as substrates replacing glucose in many tissues and also as signal substances in the regulation of energy metabolism.
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PMID:New aspects of ketone bodies in energy metabolism of dairy cows: a review. 901 Nov 47

Four groups of 6 cows were used to determine the effects of body condition on induction of ketosis. At calving, obese cows were heavier by 108 kg and had a higher body condition score by 0.74 units than did normal cows. Susceptibility to induced ketosis was evaluated by restricting dry matter intake by 20% and feeding 7% 1,3-butanediol from 15 to 49 d in milk (DIM) to one group of obese cows and to one group of normal cows. No normal or obese cows fed the control diet developed ketosis. Two normal and 2 obese cows developed ketonemia because of the induction protocol, and 1 cow in each of the two groups developed clinical ketosis. Obese cows lost 59% more body weight during the first 14 DIM than did normal cows, and cows fed the restricted diet plus 7% 1,3-butanediol lost 15% more body weight than did cows fed the control diet during the induction period. Concentrations of nonesterified fatty acids increased at parturition, peaked at 7 to 14 DIM, and returned to prepartum concentrations by 21 DIM. Plasma beta-hydroxybutyrate concentrations increased after calving and was increased additionally by the induction protocol. At the onset of lactation, plasma insulin decreased, plasma glucagon increased, hepatic triacylglycerols increased, and hepatic glycogen decreased. The incidence of ketonemia and clinical ketosis was the same for obese and normal cows, but, on the basis of changes of blood and liver composition, incidence of ketosis would probably increase if obese cows were overfed throughout the entire dry period.
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PMID:Metabolic characteristics of induced ketosis in normal and obese dairy cows. 927 95

The purpose of this investigation was to study the metabolic situation in clinical cases of bovine ketosis and to diagnose additional diseases. Extensive clinical examination, clinical biochemistry, haematology and fine-needle aspiration biopsy of liver was performed on 17 ketotic and eight control dairy cows in the field, and on seven hospitalized hyperketonaemic fatty liver patients. Additional findings in the ketotic group were heat (n = 7), indigestion (n = 5), endometritis (n = 2), cystic ovaries (n = 1), and mastitis (n = 1), and in the fatty liver group displaced abomasum (n = 4), abomasal ulcers (n = 3), mastitis (n = 2), laminitis (n = 1), bronchopneumonia (n = 1), and hypomagnesaemia (n = 2). There were no additional findings in the control group. Aspartate aminotransferase (AST) and creatine kinase (CK) were elevated in the ketosis and fatty liver groups. Total bilirubin, gamma-glutamyl transferase (GGT) and glutamate dehydrogenase (GD) were elevated in the fatty liver group and in some animals in the ketosis group. Total bile acid was not different between the groups. The free fatty acid/cholesterol ratio was higher in the fatty liver group compared with the control and ketosis groups. There was no or only slight fatty degeneration of the liver cells in the control and ketosis groups. Glucose and insulin preinjection concentrations and changes from basal values after glucagon injection were significantly lower in the ketosis group if compared with the control group. The responses in the fatty liver animals after glucagon injection were more heterogeneous than in the control and ketosis animals, a sign of disturbance in the metabolic adaptation, which together with high free fatty acid (FFA) levels can lead to fatty liver in cows with concurrent diseases.
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PMID:Glucose and insulin responses to glucagon injection in dairy cows with ketosis and fatty liver. 946 72

In summary, amylin, via its hormonal actions, may be relevant to the treatment of both forms of diabetes, and, paradoxically, via its amyloidogenic properties, may also be relevant to the pathogenesis of NIDDM. Amylin potently inhibits postprandial glucagon secretion. The absence of this action could contribute to the hyperglucagonemia and subsequently, excessive endogenous glucose production, fasting hyperglycemia, and propensity to ketosis seen in insulinopenic diabetes. Restoration of normal glucagon secretion by amylin replacement therapy could therefore be therapeutically important in treatment of insulin-dependent diabetes mellitus. Amylin potently inhibits gastric emptying. This action is consistent with a physiologic role of amylin to regulate carbohydrate absorption. Of peptides known to be secreted in response to ingested carbohydrate, only amylin and glucagon-like peptide-1 are reported to inhibit gastric emptying at near-physiologic concentrations, and could therefore participate in nutrient-mediated feedback control of carbohydrate release from the stomach. Amylin reduces food intake in rodents. This action, which synergizes with a similar action of CCK, could reflect a role as short-term peripheral satiety agent. Amylin alone or in combination with CCK may be useful in moderating caloric intake in obesity and other metabolic disorders. Although insulin has been extensively studied as a therapy and as a controller of nutrient storage and metabolism, the role of its beta-cell partner, amylin, has been largely unrecognized. In contrast to the nutrient disposal and storage role of insulin, amylin appears to more generally address the opposite side of the energy balance equation, the assimilation of nutrient.
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PMID:Roles of amylin in diabetes and in regulation of nutrient load. 964 95

Plasma beta-hydroxybutyrate concentrations were measured in the offspring of rats that were fed either a control (20% protein) diet or low-protein (8% protein) diet during pregnancy and lactation. Low-protein offspring had significantly lower plasma beta-hydroxybutyrate compared with controls in the fed state (P < .04) and after fasting for 24 hours (P < .001) and 48 hours (P < .04). There were no differences in blood glucose, acetoacetate, plasma glucagon, cholesterol, or glycerol between control and low-protein offspring. However, plasma nonesterified fatty acids (NEFAs) were significantly higher in low-protein offspring in the fed state (P < .05). In contrast, plasma triglycerides and insulin were significantly lower in low-protein offspring compared with controls when fed (P < .001) and after a 24-hour fast (P < .001). These results suggest that poor maternal and early postnatal nutrition can have long-term effects on ketone body metabolism in the offspring during adulthood. This apparent ketosis resistance is similar to that observed in some forms of human diabetes.
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PMID:Ketosis resistance in the male offspring of protein-malnourished rat dams. 986 72

We performed prospective study to determine whether the increase of calories with preoperative oral intake will prevent ketosis due to preoperative starvation in children receiving afternoon surgery. Twenty five children (aged 3 to 9 years) for elective minor surgery under general anesthesia with sevoflurane and nitrous oxide were divided into morning surgery group and afternoon surgery group, and the latter was divided into 2 groups according to calories contained in the clear fluid. The calorie of the clear fluid in the afternoon group P was 0.24 kcal.ml-1, and that in the afternoon group A was 0.48 kcal.ml-1. The calorie of the clear fluid in the morning group was 0.48 kcal. ml-1. The levels of blood glucose, blood ketone body, plasma free fatty acids (NEFA), insulin, glucagon and cortisol were measured before and during intravenous infusion in three groups. The urinary catecholamine excretion was measured in the urine collected from 18:00 on the day before operation day until the start of anesthesia. There were no significant differences in the levels of blood glucose, NEFA, insulin, glucagon, cortisol and urinary catecholamine excretion. But the level of blood ketone body only in the afternoon group P was significantly higher than that in the morning group. But the levels of NEFA before infusion were higher than average in 40-60 percent of patients of each group. These data suggest that the increasing preoperative calories with oral intake will prevent ketosis due to preoperative starvation in the afternoon group as well as in the morning group. But the short duration of starvation only can not prevent lipolysis completely.
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PMID:[The effect of calories of preoperative oral intake on the glucose metabolic response in children]. 1033 32


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