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)

Rat liver was perfused in vitro with Krebs-Henseleit-medium and albumin at 25 degrees C in a recirculating system without hemoglobin over a period of 120 min. The following basic parameters for characterization of isolated liver perfusion were recorded: medium-pO2 prior and after liver passage, flow-rate, pH, and hepatic O2-consumption. Beyond this, concentration of lactate and pyruvate, hepatic glucose production, activity of aspartate-aminotransferase, leucine-aminopeptidase and acylase as well as concentration of K+-ions in the perfusion fluid were measured. In dependence on nutrition state of liver donors (fed or starved rats) the rate of glycogenolysis or rate of lactate-stimulated gluconeogenesis was calculated. The endogenous glycogenolysis can be blocked by an in vivo injection of propranolol. The propranolol-inhibited glycogenolysis can be stimulated by an in vitro glucagon application.
 ...
PMID:[Characterization of the functional state of the in vitro Hb-free perfused rat liver]. 733 31

The role of the cellular redox state in the hormonal stimulation of gluconeogenesis was studied in hemoglobin-free perfused rat liver, by fluorimetric measurement of the redox states of intracellular pyridine nucleotides. The maximum rate of glucose production from lactate/pyruvate mixture was observed with a lactate/pyruvate ratio of 10/1, which corresponds to the ratio observed in vivo. Increased reduction of pyridine nucleotides on infusion of ethanol or octanoate was associated with an increased production of glucose from pyruvate, whereas glucose production from lactate decreased. Stimulation of gluconeogenesis from lactate by glucagon was affected by the lactate/pyruvate ratio; a decrease of the lactate/pyruvate ratio resulted in a decrease of the efficacy of glucagon. Stimulation by glucagon of glucose production from pyruvate was abolished during octanoate infusion, although it was still observable during ethanol infusion. In contrast to glucagon, the stimulatory effect of norepinephrine on gluconeogenesis was unaffected by the ratio of lactate to pyruvate. Norepinephrine in the presence of octanoate and ethanol still induced stimulation of glucose production from lactate and pyruvate, which was always accompanied by a transient reduction of pyridine nucleotides. The results demonstrate that the regeneration of NADH in the cytosol is one of the regulatory factors in gluconeogenesis, and that the effects of glucagon and norepinephrine on gluconeogenesis and on the redox state of pyridine nucleotides are not identical.
 ...
PMID:Intracellular redox state and stimulation of gluconeogenesis by glucagon and norepinephrine in the perfused rat liver. 735 25

A murine diabetes mellitus induced with a new diabetogenic variant (DK-27) which we isolated from the M variant of the encephalomyocarditis (EMC) virus was characterized. Male DBA/2 mice (9.5 weeks old) were infected with various infectious doses of DK-27 intraperitoneally. Blood glucose and insulin levels were examined in association with the viral replication. Pancreatic pathology and hormone contents and stable hemoglobin A1c (St-A1c) levels were also examined on the final day of observation (35 days of post-infection). In infected mice, blood glucose levels rapidly elevated at 72 hr, slightly decreased between 7 and 10 days and finally became sustained hyperglycemia. On the other hand, blood insulin levels elevated at 48 hr, promptly decreased, and subsequently became sustained hypoinsulinemia. Viral replication in pancreases reached the highest titers at 48 hr and rapidly disappeared with all infectious doses used. Pancreatic insulin contents in infected mice were not detectable, and glucagon contents were not affected. In pathological examination, atrophy of islets and marked diminution of B-cells were observed, and A-cells occupied the major part of an infected islet. St-A1c levels reflected lasting hyperglycemia. These findings show that DK-27 causes insulin-dependent diabetes mellitus by the specific and direct destruction of pancreatic B-cells in susceptible mice. Such a diabetic model mouse will be useful for therapeutic studies.
 ...
PMID:Characterization of insulin-dependent diabetes mellitus induced by a new variant (DK-27) of encephalomyocarditis virus in DBA/2 mice. 755 22

In the University of Pittsburgh experience, the most successful setting for human islet allografts is in patients undergoing upper abdominal exenteration with total pancreatectomy and liver transplantation for the indication of malignancy (cluster). In this group of patients 6/11 were insulin-independent for long periods. We report herein the metabolic course or the longest survivor (> 3 years). This patient has been free of exogenous insulin since the third postoperative month and has sustained her body weight without total parenteral nutrition since the 4th postoperative month. The patient has some postprandial hyperglycemia but average capillary glucoses are near-normal to normal as are glycosylated hemoglobin values. The clearance of glucose during the administration of an intravenous glucose load has been well preserved and is currently normal. C-peptide stimulates significantly in response to intravenously injected glucose. The absolute levels of stimulation during the test have declined possibly related to improvements in renal function, decreased immunosuppression or the natural history of cells transplanted into the portal site. The kinetics of the C-peptide response to intravenously injected glucose shows a persistent abnormality of first-phase insulin release and a prolonged second phase release. Basal glucagon levels are low but stimulate to a mixed meal. This patient's results demonstrate long-term function of islet cells from a single donor transplanted into the portal vein using FK506 as an immunosuppressant agent.
 ...
PMID:Long-term (> 3-year) insulin independence in a patient with pancreatic islet cell transplantation following upper abdominal exenteration and liver replacement for fibrolamellar hepatocellular carcinoma. 770 83

In an attempt to rest the beta cells of newly diagnosed children with type I diabetes mellitus (IDDM) and thus possibly preserve beta cell function, ten children were given Octreotide, a somatostatin analog, for the first 21 days after diagnosis. Ten age-matched diabetic children served as controls. Although there were no differences in either insulin requirements or in hemoglobin A1 levels, there were significant increases in the glucagon-stimulated C-peptide levels of the experimental group at six and 12 months after diagnosis, compared to control patients.
 ...
PMID:A randomized trial of a somatostatin analog for preserving beta cell function in children with insulin dependent diabetes mellitus. 773 71

Diabetes mellitus is one of the main endocrinological disease complicating the course of thalassemia major. This study aimed evaluate beta-cell secretion in 24 patients with thalassemia major attending the hematological Day Hospital at the Pediatric Clinic in Modena where transfusion therapy is performed in all thalassemic patients so as to maintain minimum hemoglobin levels above 10.5 g/dl, together with intensive ferrochelating therapy (desferrioxamine 50-60 mg/kg/die s.c. 6 days a week). A C peptide challenge with glucagon was performed in three patients already receiving insulin therapy for diabetes mellitus; this unexpectedly revealed a slight residual beta-cell secretion. An intravenous glucose tolerance test (IVGTT) was performed in the remaining 21 non-diabetic patients, with widely varying findings regarding insulin secretion: from below 50 microUl/ml in 5 patients to above 200 microUl/ml in 5 patients, and between 50 and 150 microUl/ml in the remaining 11 patients. This study therefore confirmed that insulin secretion frequently alters in thalassemic patients. Moreover, insulin secretion is not correlated to ferritinemia or influenced by familiar diabetes or patient age.
 ...
PMID:[Beta-cell secretion in patients with thalassemia major]. 779 13

Children with long-standing IDDM have impaired counterregulatory responses to hypoglycemia. To determine whether children with new onset IDDM also have altered counterregulation, we studied the counterregulatory responses to hypoglycemia in twenty children with new onset IDDM (5-6 days, age 12.6 +/- 2.9 yr, mean +/- SD), and compared these responses to 47 subjects with long-standing IDDM (duration 7.8 +/- 3.6 yr, age 15.3 +/- 2.5 yr) and 21 controls (age 14.2 +/- 2.8 yr). Six new onset subjects were restudied three months later during their remission. Glucose nadir in new onset (2.7 +/- 0.1 mmol.l-1) was similar to controls (2.4 +/- 0.1 mmol.l-1), but was higher than in long-standing IDDM (2.2 +/- 0.1 mmol.l-1). Both groups of diabetic subjects had lower glucagon responses to hypoglycemia than controls (p < 0.005). Glucagon responses in new and long-standing diabetes did not differ. Epinephrine was diminished in new IDDM compared to controls (p < 0.01). Glucose recovery was faster in new onset than in long-standing IDDM (p < 0.001) and the same as in controls. Responses remained diminished 3 months after diagnosis despite increased C-peptide and lower glycosylated hemoglobin. Thus, children with IDDM have diminished counterregulatory responses to hypoglycemia at diagnosis, that are similar to those in long-standing IDDM. The reasons for this impairment and its clinical application in childhood require further investigation.
 ...
PMID:Impaired counterregulatory hormone responses to hypoglycemia in children and adolescents with new onset IDDM. 782 Feb 18

We examined the effect of intravenous (i.v.) tolbutamide administration on glucose and hormone levels in cystic fibrosis (CF) patients with impaired first-phase insulin secretion and oral glucose tolerance (oral glucose tolerance test [OGTT]) and compared them with CF patients with only an impaired first-phase insulin secretion and healthy control subjects. Five CF patients with an impaired OGTT, ie, a serum glucose value of 7.8 mmol/L or greater 120 minutes after an oral glucose load (group I), five CF patients with a normal OGTT, ie, a serum glucose not exceeding 7.8 mmol/L 120 minutes after oral glucose (group II), and five healthy control (CON) subjects underwent IV glucose tolerance tests with glucose alone (IVGTT) and glucose administered in conjunction with tolbutamide ([IVTTT] 25 mg/kg; maximum dose, 1 g). Serum glucose levels were measured using the glucose oxidase method; insulin, C-peptide, and glucagon levels were measured by the double-antibody radioimmunoassay (RIA) technique. Serum immunoreactive trypsin (IRT) and hemoglobin A1 (HbA1) levels and height and weight were measured for each subject, and in addition, pulmonary function was assessed in those with CF. There were no significant differences in the area under the curve (AUC) for glucose or glucose or glucagon levels or the serum glucose disappearance rate (k value) between group I, group II, or CON subjects during the IVGTT. First-phase insulin and C-peptide secretion was abnormal during IVGTT and IVTTT in the CF groups: in group I it was severely impaired, whereas in group II it was between group I and CON values. During the IVTTT serum glucose levels and glucose k values were not significantly altered in any of the three groups as compared with the IVGTT.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Tolbutamide causes a modest increase in insulin secretion in cystic fibrosis patients with impaired glucose tolerance. 785 58

Insulin antibodies (IA) are detectable in the sera of most insulin-treated patients with diabetes mellitus. Antibodies to exogenous insulin sometimes cause clinical symptoms of insulin resistance, allergy, and local lipoatrophy. Although the frequency of these complications has diminished with the use of highly purified porcine insulin or recombinant human insulin, there are some patients with high titer of IA. Autoantibodies to insulin (IAA) are also described. IAA has been reported to be in association with both insulin-dependent diabetes mellitus (IDDM) and polyendocrine autoimmune disease. For many years these antibodies have been measured by radiobinding assay (RBA) in which the complexes are precipitated non-specifically by polyethylene glycol. In the present study we developed a rapid and quantitative enzyme-linked immunosorbent assay (ELISA) method for measuring IA and IAA using recombinant human insulin antigen. We applied this method to the samples obtained from patients with diabetes mellitus and autoimmune thyroid disease and then compared the results with those obtained from the RBA method. The calibration curve for ELISA was derived from the dilution curve of a single serum from a patient positive for insulin antibody, and the results were expressed arbitrarily as ELISA UNIT. The calibration curve was approximately linear on the log-log scale within the range of 0.1-2.0 at optical density (OD)450nm, (6.25-200 ELISA UNIT). The intra-assay (CV = 2.3-3.1%) and inter-assay (CV = 2.8-7.2%) precisions were acceptable. Recovery rate varied from 74.5% to 118.5% and dilution experiments showed good linearity. Specificity was demonstrated by substituting purified human IgG for the test serum and glucagon for insulin. Except for hemoglobin, coexisting substances in serum had almost no effect on ELISA. The range of ELISA UNIT (Mean +/- SD) of 83 normal sera was 12.7 +/- 4.6. Positivity for IA by ELISA (> normal Mean + 3SD) was 11 out of 58 (19.0%) and 26 out of 55 (47.3%) in patients with IDDM and with non-insulin-dependent diabetes mellitus (NIDDM) who were treated with insulin, respectively. Positivity for IAA by ELISA was 5 out of 173 (2.8%) and 1 out of 20 (5.0%) in patients with NIDDM without insulin therapy and hyperthyroidism due to Graves' disease, respectively. However, by RBA, we detected 4 other cases positive for IAA in NIDDM without insulin therapy and one case in Graves' disease. The present study demonstrates that the newly developed method of ELISA using recombinant human insulin antigen is clinically useful for measuring IA and IAA.
 ...
PMID:[The measurement of insulin antibodies and insulin autoantibodies by enzyme-linked immunosorbent assay using recombinant human insulin antigen and its clinical application]. 795 8

To evaluate the hypothesis that lactate supply is essential to maintain euglycemia during iron deficiency, female Sprague-Dawley rats were assigned to iron-sufficient (50 mg Fe2+/kg diet, +Fe), or iron-deficient (15 mg Fe2+/kg diet, -Fe) dietary groups and were injected with a specific beta 2-adrenergic inhibitor, ICI 118,551 (1.0 mg/kg body wt). Rats were studied at rest or after 30 min of running at 13.4 m/min 0% grade. Dietary iron deficiency decreased hemoglobin concentration 38%, but resting arterial concentrations of glucose ([Glc]), lactate ([La]), or alanine ([Ala]) were unaffected. Administration of ICI 118,551 (beta 2-blockade) decreased [La] and [Glc] 52 and 32% in resting -Fe rats, respectively. beta 2-Blockade attenuated the exercise-induced rise in [La] and decreased [Glc] 31% in exercising -Fe rats. [Ala] were unaffected by iron deficiency or exercise but decreased 24 and 18% because of beta 2-blockade in resting and exercising +Fe rats. Iron deficiency depleted resting liver glycogen concentration 45%, with no additional effect of exercise or beta 2-blockade. beta-Blockade decreased arterial insulin and increased arterial glucagon concentrations in resting -Fe and +Fe rats. During exercise glucagon concentration increased significantly more in -Fe than +Fe rats. Decreased arterial [La] with a corresponding decrease in arterial [Glc] in response to beta 2-blockade support the contention that lactate supply is critical to maintenance of euglycemia in -Fe rats at rest and during exercise.
 ...
PMID:Lactate is essential for maintenance of euglycemia in iron-deficient rats at rest and during exercise. 809 76


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>