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)

Insulin and glucagon secretions were studied during oral glucose tolerance testing and arginine infusion in 13 patients with cystic fibrosis. Two groups of patients were identified; Group I (N=6) whose OGTT was entirely normal and Group II (N=7) who had some abnormality in glucose during OGTT. In each group basal glucagon concentrations were normal and supressed appropriately (p less than 0.05) after glucose; insulin responses were attenuated and the peak responses delayed. During arginine stimulation, insulin secretion was impaired in each group. However, glucagon secretion was diminished only in Group II. Thus, insulinopenia was found in both groups and hyperglucagonemia was not found as a contributory factor to the hyperglycemia in Group II.
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PMID:Pancreatic alpha and beta cell functions in cystic fibrosis. 32 39

The glucagon and insulin responses to intravenous arginine were studied in 17 children with cystic fibrosis and in 9 control children. It was found that the overall secretion of insulin was diminished; however, four of the CF children did have a normal output. The glucagon responses did not parallel those of insulin. The glucagon output varied in the CF children--seven had normal, four excessively high and six low output. Three of the four children with extremely high output had more severe disease and were below the third centile on the weight chart. These four had a fasting hypoglycaemia and also a very low glucose and insulin response. We have confirmed diminished insulin secretion in cystic fibrosis, but diminished glucagon secretion was only noted when some insulin secretion was preserved. The high levels of glucagon seen in the most insulin deficient subjects may be derived from extrapancreatic sources, or may be associated with 'stress' reaction in these patients who also had most severe pulmonary involvement. The data would be consistent with diminished glucagon and insulin secretion from the pancreas but as the disease progresses an excessive secretion of extra pancreatic glucagon results.
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PMID:Insulin and glucagon response to arginine infusion in cystic fibrosis. 84 41

Pancreatic endocrine function was studied in 50 patients with cystic fibrosis (CF) and 15 healthy controls by measuring glucose, insulin, C-peptide, glucagon and gastro-inhibitory polypeptide responses to an oral glucose tolerance test (OGTT). Biochemical and clinical parameters were also measured, including glycosylated hemoglobin A1, serum immunoreactive trypsin, fasting urinalysis, pulmonary function, percentage body fat and 3-day dietary records. According to National Diabetes Data Group (NDDG) criteria, 6 CF patients had impaired glucose tolerance (ICF), with elevated serum glucose concentrations and reduced and delayed insulin secretion compared with control (CON) subjects, although none were overtly diabetic. Although the remaining 44 CF patients (NCF) did not meet NDDG criteria for impaired glucose tolerance, mean area under the concentration curve (AUC) for glucose was greater than control values and AUC for insulin diminished. HbA1 levels in the 2 CF groups were greater than that of controls subjects, but there was little difference between ICF and NCF groups. C-peptide levels paralleled those of insulin for the 3 groups throughout OGTT. There was little difference in GIP secretion between groups, and the enteroinsular axis was intact in the control and NCF groups and slightly increased in the ICF group. Basal glucagon concentrations and AUC for glucagon during OGTT were similar for the 3 groups, but glucose-induced glucagon suppressibility i.e., basal to nadir change in each subject, was reduced in the ICF group. Serum IRT concentration was significantly lower in the ICF and NCF groups compared to control subjects, and was lowest in the ICF group. A strong correlation was observed in the ICF group between FEF25-75 and AUC for insulin, as well as HbA1 level and AUC for glucose. The prevalence of impaired glucose tolerance in 50 CF patients was 12%. Despite extensive comparisons of biochemical and clinical parameters with endocrine function in this population, we were unable to define reliable criteria for predicting glucose intolerance.
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PMID:Postprandial hyperglycemia and pancreatic function in cystic fibrosis patients. 184 15

To characterize pancreatic endocrine secretion and to examine interrelationships among alterations in alpha, beta, and pancreatic polypeptide cell function in patients with cystic fibrosis (CF), we studied 19 patients with exocrine insufficiency (EXO), including 9 receiving insulin therapy (EXO-IT); 10 patients with no exocrine insufficiency (NEXO); and 10 normal control subjects. First-phase C-peptide response to intravenously administered glucose was significantly impaired in CF patients with exocrine insufficiency (EXO-IT = 0.02 +/- 0.01; EXO = 0.11 +/- 0.02; NEXO = 0.25 +/- 0.05; control subjects = 0.30 +/- 0.04 nmol/L). Lowering fasting glucose levels with exogenous insulin administration in EXO-IT did not improve beta cell responsivity to glucose. The C-peptide response to arginine was less impaired (EXO-IT = 0.12 +/- 0.02; EXO = 0.15 +/- 0.02; NEXO = 0.23 +/- 0.06; control subjects = 0.28 +/- 0.04 nmol/L). Alpha cell function, measured as peak glucagon secretion in response to hypoglycemia, was diminished in EXO but not NEXO (EXO-IT = 21 +/- 10; EXO = 62 +/- 19; NEXO = 123 +/- 29; control subjects = 109 +/- 12 ng/L). Despite diminished glucagon response, EXO patients recovered normally from hypoglycemia. Peak pancreatic polypeptide response to hypoglycemia distinguished CF patients with exocrine insufficiency from those without exocrine insufficiency (EXO-IT = 3 +/- 2; EXO = 3 +/- 1; NEXO = 226 +/- 68; control subjects = 273 +/- 100 pmol/L). Thus CF patients with exocrine disease have less alpha, beta, and pancreatic polypeptide cell function than CF patients without exocrine disease. These data suggest either that exocrine disease causes endocrine dysfunction in CF or that a common pathogenic process simultaneously and independently impairs exocrine and endocrine function.
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PMID:Pancreatic endocrine function in cystic fibrosis. 201 25

As a result of the improvement in life-expectancy in cystic fibrosis patients, simultaneous presence of cystic fibrosis and diabetes mellitus is no longer exceptional. In teenagers and young adults with cystic fibrosis, the prevalence of insulin-dependent diabetes mellitus (IDDM) is 7 to 10%. Fifty percent of cystic fibrosis patients have impaired glucose tolerance. These prevalences increase with advancing age. Insulin deficiency is a consistent feature. An endocrine pancreatic deficiency thus exists in addition to the exocrine pancreatic deficiency, as demonstrated by the fall in glucagon and pancreatic polypeptide productions. Development of insulin dependency is associated with deterioration in clinical status and indicates an adverse prognosis. Although in cystic fibrosis patients diabetes mellitus seems to occur as a result of different pathophysiologic mechanisms than those involved in autoimmune IDDM, the risk of degenerative complications is similar in both conditions. It follows that early detection of diabetes mellitus and appropriate insulin treatment are warranted in cystic fibrosis patients.
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PMID:[Glucose intolerance and diabetes during cystic fibrosis]. 206 59

The incidence of fasting hyperglycemia and diabetes mellitus (DM) in older patients with cystic fibrosis (CF) is reported to be 8%, but few quantitative studies of the islets of Langerhans in this disease have been done. Three groups of patients were studied in this morphometric autopsy analysis: patients with CF and insulin-dependent DM (n = 7), normoglycemic patients with CF (n = 4), and age-matched adolescents and young-adult controls (n = 11). The islets of Langerhans were stained with immunoperoxidase for insulin, glucagon, and somatostatin. The percentage of the total islet surface area occupied by each immunoperoxidase positive cell type was determined by a point-counting method. The mean percent surface area occupied by insulin-producing cells (28.3%) in diabetics with CF was significantly less than normoglycemics with CF (46.7%) and controls (53.4%). The mean percent surface area occupied by glucagon-producing cells was similar in all three groups: 21.9% in CF diabetics, 25.4% in normoglycemics with CF, and 22.4% in controls. The mean percent surface area occupied by somatostatin was increased in both CF groups compared with controls: diabetics with CF, 29.3%; normoglycemics with CF, 26.2%; and controls, 15.5%. These findings correlate with published clinical endocrine studies of hyperglycemia in CF. Endocrine cell quantitation in diabetics with CF differs from that in both juvenile (type 1) and adult-onset (type 2) DM.
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PMID:Islets of Langerhans in adolescents and adults with cystic fibrosis. A quantitative study. 287 72

Twenty-three patients with recent onset Type 1 (insulin-dependent) diabetes in whom residual insulin secreting B cells were present and 12 patients with disease of more prolonged duration (maximum 9 years), 8 of whom had residual B cells, were studied. Aberrant expression of Class II major histocompatibility complex molecules was demonstrated immunohistochemically on insulin secreting B cells in 21 out of 23 patients with recent onset disease and 6 of the patients with more prolonged disease. No such expression was seen on glucagon secreting A cells or somatostatin secreting D cells. Islets where there was marked hyperexpression of Class I major histocompatibility complex molecules on islet endocrine cells were seen in all cases in which residual B cells were present. Ninety-two per cent of insulin containing islets but only 1% of insulin deficient islets exhibited this phenomenon (p less than 0.001, Chi-squared test). There was evidence to suggest that both these abnormalities of major histocompatibility complex expression preceded insulitis within a given islet. They also appeared to be unique to Type 1 diabetes, being absent in pancreases of patients with Type 2 (non-insulin-dependent) diabetes, chronic pancreatitis, cystic fibrosis, graft-versus-host disease and Coxsackie B viral pancreatitis. The development of autoimmunity to B cells in Type 1 diabetes may be a "multistep" process in which abnormalities of major histocompatibility complex expression on islet endocrine cells are crucial events.
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PMID:Aberrant expression of class II major histocompatibility complex molecules by B cells and hyperexpression of class I major histocompatibility complex molecules by insulin containing islets in type 1 (insulin-dependent) diabetes mellitus. 330 84

Patients with cystic fibrosis of the pancreas show an incidence of diabetes mellitus tenfold higher than is found in the general pediatric population. Considering this fact glucagon and insulin responses to oral glucose and intravenous arginine were studied in 22 CF children and adolescents. Some investigated patients had suffered from the disease for ten years and more. On the one hand the results show that pancreatic alpha cell function is normal. The kinetics of endogenous glucagon release are unaltered. On the other hand the data reveal that there is only a defect in the beta cell function consisting in a delayed insulin release selective to glucose whereas responsiveness to other stimuli for example tolbutamide and arginine is undisturbed. Furthermore there is a diminution in insulin-output to oral glucose as well as to intravenous arginine. Yet in patients with normal oral glucose tolerance endogenous insulin secretion is significantly reduced. Their regular carbohydrate tolerance may be a function of the patient's ability to maintain increased receptor numbers in the face of hypoinsulinemia. Despite greater quantities of secreted hormone a degree of relative peripheral insulin insensitivity has developed in the presence of hyperglycemia. This may be a consequence of impaired affinity of the specific target cell receptors. The insulin secretion pattern is proven to be identical to that of chemical diabetes mellitus in adults. Quantitative diminution in arginine stimulated insulin-output has been found to be independent of the degree of carbohydrate intolerance.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Endocrine pancreas function in mucoviscidosis]. 388 47

We evaluated carbohydrate tolerance in nine thin cystic fibrosis (CF) patients and in six controls, measuring responsiveness to the following insulinotropic secretagogues: oral glucose, IV glucose, and IV tolbutamide. Glucose responses segregated patients into two groups: Group I with normal carbohydrate tolerance associated with normal to slightly increased insulin responses, and Group II with impaired carbohydrate tolerance associated with insulinopenia. This latter group included one patient with frank diabetes. The CF patients demonstrated a significant positive correlation between insulin secretion, in response to each secretagogue, and pancreatic exocrine function as measured by serum pancreatic amylase isoenzyme concentration. Pancreatic alpha-cell function, as reflected by basal plasma glucagon concentrations, also correlated well with exocrine function in the CF patients, excluding the diabetic individual. The enteroinsular axis of the CF group was intact as reflected by normal plasma gastric inhibitory polypeptide concentrations in Group I and by elevated levels, basally and in response to oral glucose, in the insulinopenic Group II patients. Furthermore, those patients with impaired tolerance demonstrated a greater magnitude of insulinopenia compared to controls following IV glucose and possibly IV tolbutamide, than following oral glucose. Thus, these data suggest that loss of carbohydrate tolerance in patients with CF, like that seen with classical chronic pancreatitis, 1) parallels the loss of exocrine function, 2) is associated with appropriate enteroinsular signaling, and 3) can be detected earlier or more easily following testing with direct IV secretagogues than following oral glucose stimulation.
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PMID:Carbohydrate tolerance in cystic fibrosis is closely linked to pancreatic exocrine function. 608 38

Regulation of pancreatic exocrine secretion is comprised of a complex interplay between hormonal and nervous mechanisms. Stimulatory gut hormones which act via the circulation include secretin, CCK, gastrin and bombesin, while VIP operates through peptidergic nervous release. Pancreatic polypeptide and glucagon are two examples of circulating inhibitory hormones while inhibition by somatostatin is through a paracrine release mechanism. Although the effects of vagal cholinergic nerves have been previously thought to be indirect through hormone release evidence is now accumulating for a direct role. Altered hormone release has been noted in chronic pancreatic insufficiency, cystic fibrosis and coeliac disease and may contribute in an important way to the pathophysiology of these malabsorptive disorders.
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PMID:Neuro-hormonal control of pancreatic function in man and its failure. 613 50


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