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)

As part of a randomized, prospective trial in subjects with insulin-dependent diabetes assigned to either continuous subcutaneous insulin infusion (CSII) or to their unchanged conventional insulin treatment (CIT) for 8 mo, patients completed questionnaires dealing with general responses and clinical and technological problems. Although there was no significant difference between treatment groups with respect to the number of patients experiencing severe hypoglycemia (i.e., requiring intravenous glucose or intramuscular glucagon injection), there were nine episodes in six patients during CSII compared with one episode during CIT. Diabetic ketoacidosis occurred significantly more often in the CSII group (nine episodes in eight patients) than in the CIT group (no episodes). A number of CSII-related failures occurred, including omission of premeal bolus, needle dislodgement, pump accidentally turned off, and leakage at the infusion site. At 8 mo, 85% of CSII-treated patients wished to continue indefinitely on the pump, and almost all would continue with self-monitoring of blood glucose even if they stopped CSII.
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PMID:Conference on insulin pump therapy in diabetes. Multicenter study of effect on microvascular disease. The pump life. Patient responses and clinical and technological problems. 389 27

Insulin therapy was withdrawn from 15 well-controlled type I diabetic subjects for no longer than 18 h to examine the sequence with which 13,14-dihydro-15-keto-PGE2 (PGE-m), glucagon, norepinephrine, and epinephrine increased in circulating blood in diabetic subjects becoming ketoacidotic. Fourteen of 15 patients had increments in PGE-m; 12/12, 12/15, and 13/15 had increments in glucagon, norepinephrine, and epinephrine, respectively. Six of the 15 patients developed mild diabetic ketoacidosis (DKA) by 12-18 h; all had nonmeasurable C-peptide levels. This DKA group had significantly greater increments of PGE-m (835 +/- 130 versus 276 +/- 111 pg/ml, mean +/- SEM, P less than 0.01) but not glucagon, norepinephrine, or epinephrine compared with the 9 non-DKA patients. In the DKA group, there were significant PGE-m and glucagon increments in the circulation by 3 h, significant norepinephrine increments by 9 h, and epinephrine increments in 5/6 patients by 12 h (not statistically significant) of insulin withdrawal. These studies document that (1) PGE-m accumulates in the circulation during DKA, (2) PGE-m and glucagon increase before catecholamines, and (3) PGE-m, glucagon, and catecholamine levels promptly return to normal levels when insulin therapy is reinstituted. It is suggested that elevated PGE-m levels early in the onset of DKA may represent a host-defense mechanism.
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PMID:Prostaglandin E2 metabolite levels during diabetic ketoacidosis. 392 65

The development of a glucagon radioimmunoassay with a relatively high degree of specificity for pancreatic glucagon made possible studies of alpha cell function in healthy nondiabetic subjects and in patients with diabetes mellitus. In the former group mean fasting plasma glucagon averaged 108 mumug/ml (SEM +/-10). In 12 juvenile-type diabetics fasting glucagon averaged 110 (+/-9) and in 33 adult-type diabetics the average was 114 (+/-8). The diabetic averages did not differ significantly from the nondiabetic subjects; however, when hyperglycemia was induced by glucose infusion in the nondiabetic subjects so as to simulate the fasting hyperglycemia of the diabetics, mean glucagon fell to 57 mumug (+/-8), which was significantly below the diabetic mean. In 28 healthy subjects the infusion of arginine elicited a rise in glucagon of at least 100 mumug/ml with a peak level averaging 331 mumug/ml (+/-22) at 40 min. This response to arginine was diminished but not abolished during hyperglycemia induced by simultaneous glucose infusion. In everyone of 45 diabetic subjects tested the infusion of arginine elicited a rise in glucagon of at least 140 mumug/ml to levels significantly greater than in nondiabetics. The peak glucagon level in juvenile-type diabetics averaged 458 mumug/ml (SEM +/-36) and in adult-type diabetics averaged 452 mumug/ml (SEM +/-38). The glucagon response to arginine was unrelated to duration of diabetes, to body weight, type of diabetic treatment, or to other known factors. Marked hyperresponsiveness of glucagon to arginine infusion was observed in two patients with advanced Kimmelsteil-Wilson disease. Glucagon levels were markedly elevated in certain patients with severe diabetic ketoacidosis before treatment with insulin. The findings suggest that alpha cell function is inappropriately increased in diabetes mellitus and could play a significant role in the diabetic syndrome.
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PMID:Studies of pancreatic alpha cell function in normal and diabetic subjects. 498 15

Salbutamol-induced diabetic ketoacidosis having recently been reported, the authors have studied the metabolic changes produced by the drug in 6 nondiabetic patients. All patients received a 3-hour infusion of salbutamol (S) 20 z g/minm. On the following day, three of these were given somatostatin (SRIF) 100 mg/hour mixed with S infused at the same rate, whilst the remaining 3 patients received SRIF alone. On the 3rd day, patients of the first sub-group received the same infection of S and SRIF as before plus exogenous glucagon 90 ng/kg/hour. Somatostatin is know to inhibit insulin and glucagon secretion. Exogenous glucagon was given in order to reproduce the metabolic conditions of insulin-deficient diabetes mellitus. Salbutamol alone induced a small rise in blood glucose and insulin, free fatty acids, glycerol and ketonic bodies, but no changes in endogenous glucagon. SRIF alone produced no significant metabolic variations. In the presence of SRIF, all salbutamol-induced metabolic changes were increased. Adding glucagon mainly resulted in high levels of ketonic bodies. All variations correlated with each other. Thus, whilst the hyperglycaemic, lipolytic and ketogenic effects of S in non-diabetic patients are partly masked by insulin hypersecretion, they are enhanced in the absence of insulin and, to an even greater extent, by an excess of glucagon. Diabetic patients treated with salbutamol should therefore be under close surveillance and have their insulin dosage increased.
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PMID:[Metabolic risks of salbutamol in diabetic patients. A study using somatostatin (author's transl)]. 610 23

The effect of low-dose insulin infusion (4.8 U/h) in diabetic ketoacidosis was compared to that of low-dose insulin infusion (4.8 U/h) plus somatostatin (500 microgram/h IV). Treatment with insulin only in 20 patients caused normalization of blood glucose levels within 6 hours and resolution of ketoacidosis within 5 hours. During insulin plus somatostatin infusion in 7 patients, blood glucose levels returned to normal within 4 hours and acidosis was reduced within 3 hours. Correction of acidosis is the most important problem in diabetic ketoacidosis: in the severest cases cardiovascular and cerebral complications may ensue. The data presented show that addition of somatostatin to treatment with low doses of insulin reduces and resolves acidosis in a shorter time while plasma levels of glucagon and GH were concomitantly reduced.
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PMID:Somatostatin and insulin infusion in the management of diabetic ketoacidosis. 611 15

A 73-year-old man had diabetes mellitus, diarrhea, weight loss, and a rash of several years' duration. The rash, termed necrolytic migratory erythema, was the most characteristic feature and eventually suggested the diagnosis of a glucagon-secreting tumor of the pancreas. Diabetic ketoacidosis also developed in our patient, a previously unrecognized occurrence with this syndrome.
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PMID:The glucagonoma syndrome. Report of a case. 624 59

Diabetic ketoacidosis is an extremely rare manifestation of glucagonoma. We report such a case in a 72-year-old woman known to be diabetic for seven years. The patient was admitted with diabetic ketoacidosis and associated necrolytic migratory erythrema which suggested the diagnosis of glucagonoma. Plasma glucagon levels were increased (569 to 2298 pg/ml). A vascular tumor of the head of the pancreas without obvious hepatic metastases was visualised by angiography. Duodeno-pancreatectomy including the head of the pancreas led to complete recovery of the mucocutaneous lesions and the plasma glucagon level fell (229 pg/ml). The tumor had several histological characteristics suggesting malignancy and a high glucagon content on extraction. Electron microscopy showed multiple A cells and a few isolated B cells. Most of the cells showed immunoreactivity with anti-glucagon and anti-glicentine antibodies. Three months after surgery, the diabetes was again required treatment with insulin. Plasma glucagon level was again increased and chemotherapy with dimethyltriazenimidazolecarboxamide was undertaken.
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PMID:[Glucagonoma with diabetic ketoacidosis; case report]. 629 11

Diabetic ketoacidosis (DKA) is the commonest endocrine emergency encountered in clinical practice. Although in the last 3 decades the average worldwide immediate mortality has decreased from 10% to 5%, survival has not improved strikingly. The pathogenesis of DKA is currently attributed to a combination of two hormonal abnormalities--a relative insulin insufficiency and stress hormone excess (glucagon, catecholamines, cortisol and growth hormone). Withdrawal of exogenous insulin, pancreatic beta cell failure and insulin resistance are factors leading to relative insulin insufficiency. Factors leading to stress hormone excess include fasting, stress and dehydration. The combination of these two hormonal abnormalities leads to impaired carbohydrate utilization and ketonaemia which in turn results in metabolic acidosis with loss of water through acidotic breaths, rise in plasma lipids, hyperglycaemia and glycosuria leading to osmotic diuresis and further loss of water, excretion of partly neutralised ketoacids via the kidney with loss of cations (Na+ and K+). A net increase in protein catabolism which leads to an increased amino acid flux from muscle and an enhanced load of gluconeogenic precursor to the liver and a rise in blood pyruvate and lactate concentration. The prevention of either of these hormonal abnormalities will prevent the development of DKA. The successful outcome in the treatment of DKA is clearly related to the prompt recognition of the diagnosis and the precipitation factors, the severity of the initial metabolic derangements, the judicious use of fluid and electrolyte replacement, the choice, route and dosage of the insulin therapy and above all the close monitoring and meticulous clinical care of the patient throughout the entire course of the treatment. Current acceptable treatment of DKA include the following: adequate fluid replacement: low dose insulin therapy at frequent intervals; adequate potassium replacement from time of first insulin therapy with ECG monitoring; bicarbonate replacement if pH less than 7.1; broad spectrum antibiotics if infections is suspected and other supportive measures. The role of phosphate and magnesium replacement is still controversial. An awareness of the complications during the treatment of DKA including cerebral edema (paradoxical acidosis), altered central nervous system oxygenation, vascular thrombosis, shock, myocardial infarction, pancreatitis, infection, inhalation of vomitus , overhydration, underhydration , hypoglycaemia, hyperkalemia and hypokalemia all certainly help improve the morbidity and mortality of DKA.
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PMID:Current concepts of the pathogenesis and management of diabetic ketoacidosis (DKA). 633 Dec 71

The pathophysiology of beta cell failure in IDDM has not been well documented. Islet cell responsiveness (C-peptide and glucagon) to oral glucose (OGTT), intravenous glucose (IVGTT), and arginine infusion was studied sequentially in a 24-yr-old nonobese patient with IDDM in prolonged remission interrupted by an episode of diabetic ketoacidosis and followed by a second transient (6 mo) partial recovery of beta cell function. The earliest abnormality in glucose tolerance was demonstrated with the IVGTT (K = 0.77) although OGTT (F, 101: 1/2 h, 177; 7 h, 211; 1 1 h, 144; and 2 h, 111 mg/dl) and glucagon responses to glucose and arginine were normal. With the development of abnormal OGTT, glucagon failed to suppress with hyperglycemia although basal levels were not elevated. With the development of frank clinical diabetes, C-peptide did not respond to oral or i.v. glucose although stimulation in response to arginine infusion was still possible. Basal glucagon concentrations were now elevated. Thus, the failing beta cell shows a progressive deterioration in its responsiveness to various secretagogues in a sequential manner (i.v. glucose followed by oral glucose and then i.v. arginine). Abnormalities in glucagon secretion can be demonstrated early in the development of abnormal oral glucose tolerance. With more precise elucidation of the etiology of diabetes, it may be possible to intervene therapeutically in diabetic individuals who experience a remission in order to prevent further deterioration in beta cell function.
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PMID:Pathophysiology of beta cell failure after prolonged remission of insulin-dependent diabetes mellitus (IDDM). 642 54

We studied the efficacy of low-dose (0.1 U/kg/h) and high-dose (1..0 U/kg/h) insulin, given randomly to children with diabetic ketoacidosis (DKA) by continuous intravenous infusion without a loading dose. Plasma glucose reached 250 mg/dl in 3.4 +/- 0.4 h with the high-dose insulin group compared with 5.4 +/- 0.5 h with the low-dose insulin group (P < 0.01). During the first 12 h of therapy, plasma glucose fell below 100 mg/dl in 2 of 16 in the low-dose compared with 12 of 16 in the high-dose patients. The decrement of ketone bodies, cortisol, and glucagon was similar in both groups. The number of hours required for HCO3(-) greater than or equal to meq/l and arterial blood pH greater than or equal to 7.30 were not significantly different in the two groups. Hypokalemia (K < 3.4 meq/L) occurred in 3 of 16 low-dose and 10 of 16 high-dose patients. The data show that low-dose insulin, with a slower rate of glucose decrease, is as effective as a high dose for the treatment of DKA in children with less incidence of hypokalemia and decreased potential for hypoglycemia.
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PMID:Comparison of high-dose and low-dose insulin by continuous intravenous infusion in the treatment of diabetic ketoacidosis in children. 677 25


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