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)

50 HLA-typed insulin-dependent diabetics were studied at the time of diabetes onset and after 1, 2, 3 and 5 years with regard to C-peptide secretion after combined stimulation with glucose and glucagon, insulin requirement and glycaemic control index. The mean decrease of the residual B-cell reserve was observed within two years. C-peptide secretion was correlated with better metabolic control and lower insulin requirement after more than one year of diabetes duration, but had no influence on this at the time of diabetes onset. The C-peptide response sometimes varied between non response and high response in one individual from one investigation to the next. There was no prognostic value of C-peptide secretion at diabetes onset for the further development of B-cell function. We found a significantly longer persistence of B-cell function in patients who were older and in those with mild symptoms at diabetes onset. The presence of HLA B8, DR3 antigens was correlated with severe ketoacidosis at manifestation and a more pronounced destruction of B-cell function.
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PMID:5-year follow-up study of C-peptide secretion in newly diagnosed type I diabetics: relations to HLA-phenotype, insulin requirement and metabolic control. 330 71

Some patients do not fall neatly into the categories of Type 1 (insulin-dependent), Type 2 (non-insulin-dependent) or maturity onset diabetes of young people diabetes. The pedigree and characteristics of the family reported here illustrate this problem. Nine cases of diabetes are known in 4 out of 5 generations, with onset between 17-70 years. Treatment was with insulin in 5 (onset 17-29 years), tablets in 3 (onset 32-70 years), and in one diabetes occurred before the insulin era. Plasma C-peptide was 0.04-0.52 nmol/l (fasting) and 0.35-1.33 nmol/l (peak stimulation with glucagon). HLA typing, available in 7 diabetic patients showed DR2 or DR7 in all, DR4 in 2 and DR3 in none. Pancreatic islet cell antibodies were absent at diagnosis in the most recently diagnosed patient. Diabetic complications remain absent in two insulin-treated patients (duration 28 and 24 years), but have occurred extensively in the remainder. The form of diabetes in this family is therefore characterised by (a) strong family history (possible autosomal dominant with variable penetrance), (b) widely variable age of onset, (c) a variable degree of B cell reserve (d) no association with HLA DR3/4 and the presence of DR2 or DR7 and (e) no protection from complications.
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PMID:Familial diabetes mellitus with variable B cell reserve; analysis of a pedigree. 330 4

Production of and response to interleukin 2 (IL-2) were studied using peripheral blood mononuclear cells (PBMC) from 23 patients with type 1 diabetes. When compared to PBMC from 18 control subjects, mean PHA-stimulated IL-2 synthesis in the diabetic group was found unimpaired (1.2 +/- 0.1 vs 1.5 +/- 0.2 U/ml). However, 3 subgroups could be distinguished with regard to IL-2 synthesis: IL-2 production was significantly increased in 5 patients and decreased in 2 patients, while the remaining 16 diabetics produced normal levels of IL-2. The diabetic group displayed a curve of PBMC proliferation in response to a range of recombinant IL-2 which was not significantly altered. However, an abnormally high blastogenic response was detected in 5 patients, correlating to an increased percentage of Ia-bearing T lymphocytes, while a markedly low response was seen in 2 other patients. These alterations of the IL-2 system could be related duration of diabetes. Indeed, high synthesis of IL-2 was more frequent in patients with long-standing disease than in recent onset diabetics: 44% and 7%, respectively. Conversely, increased response to IL-2 was found more often in the latter group than in the former (28% vs 11%) while decreased sensitivity was seen only in the latter group (14%). No correlations were found between these results and basal or glucagon-stimulated C peptide levels, percent of glycosylated hemoglobin, presence of autoantibodies, lymphocyte subsets, or HLA typing.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Production of and response to interleukin 2 by blood mononuclear cells from some type 1 diabetic patients. 349 40

In order to study the heterogeneity of Type 2 (noninsulin-dependent) diabetes, we determined HLA antigens and measured B-cell function as C-peptide response to intravenous glucagon in 217 patients with onset of non-ketotic diabetes after the age of 40 years. Their HLA frequencies were compared with those of Type 1 (insulin-dependent) diabetic patients and of healthy blood donors. The Type 1 diabetic patients showed a typical HLA pattern, with increased frequencies of B15, DR3, DR4, B8/B15 and DR3/DR4 and decreased frequencies of B7 and DR2. The Type 2 diabetic patients could be distinguished from blood donors by increased frequencies of Cw4, DR4, DR5 and DR3/DR4, and from Type 1 diabetic patients by increased frequencies of B7, DR2, DR5 and decreased frequency of A9, Bw22 and DR4. Age at onset and body mass index were unrelated to HLA antigens, but the Type 2 diabetic patients with HLA-Cw4, DR5 and DR6 showed a strong family history for Type 2 diabetes. Type 2 diabetic patients with HLA-B8, DR4, B8/B15 and DR3/DR4 showed significantly lower C-peptide concentrations (p less than 0.05) than patients without these HLA antigens. In contrast, patients with DR5 and DRw8 presented with high C-peptide levels. Twelve patients who were positive for both DR3 and DR4 and 23 patients who were DR3/DR4 negative were followed with repeated C-peptide determinations during a period of three years. The C-peptide concentrations of the DR3/DR4 positive patients decreased during this period, whereas there was no change in C-peptide levels in the DR3/DR4 negative patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relationship between B-cell function and HLA antigens in patients with type 2 (non-insulin-dependent) diabetes. 354 54

The case of a female patient with fasting hypoglycaemia before the development of Type 1 (insulin-dependent) diabetes mellitus is reported. She presented with primary hypothyroidism, partial hypopituitarism, adrenal insufficiency and glucagon deficiency. Thyroid microsomal and gastric parietal cell antibodies were detected as well as HLA-B8, whereas islet cell antibodies were not demonstrable, even 2 years after the onset of diabetes. Plasma chromatography revealed true pancreatic glucagon (IRG3500) close to undetectable in basal samples with a questionable increase from 3 to 18 pg/ml during insulin-induced hypoglycaemia. After an overnight fast, moderate hyperaminoacidaemia was found with elevations of alanine, glycine, serine, arginine and ornithine as seen in pancreatectomized patients. It is suggested that the deficient glucagon secretion in this patient might, at least in part, have been the cause of fasting hypoglycaemia and the failure of glucose recovery following insulin-induced hypoglycaemia. Possible, the A cell deficiency was part of the polyglandular failure syndrome in this patient.
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PMID:Glucagon deficiency associated with hypoglycaemia and the absence of islet cell antibodies in the polyglandular failure syndrome before the onset of insulin-dependent diabetes mellitus: a case report. 635 16

The frequency and significance of cytoplasmic pancreatic alpha cell autoantibodies (ACA) were investigated in 2102 healthy controls, 879 patients with insulin-dependent diabetes mellitus (IDDM) who were negative for islet cell autoantibodies (ICA), and 1567 relatives of IDDM patients. ACA were found in approximately 1 in 200 people of all ages and were not significantly associated with IDDM, the IDDM-associated HLA phenotypes DR3 and DR4, or thyrogastric or adrenal autoantibodies. Of 11 ACA-positive patients studied by arginine stimulation tests, none had frank glucagon deficiency. Thus, ACA do not appear to be associated with defective alpha cell function or with IDDM.
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PMID:Pancreatic alpha cell autoantibodies and glucagon response to arginine. 637 51

The induction of a remission has been attempted in 28 patients with insulin-dependent diabetes of less than 3 months' duration by strictly normalizing glycemia either with a period of external artificial pancreas followed by continuous subcutaneous insulin infusion (22 patients) or with continuous subcutaneous insulin infusion alone (6 patients). HLA A, B and DR antigens were determined in every patient. Residual beta-cell function was evaluated by measuring C peptide and the ratio of C peptide to glycemia, and by testing the response to a glucagon stimulation before initiating and after withdrawing insulin treatment. Oral treatment with 15 mg glibenclamide and 840 mg metformin daily was administered when insulin had been stopped. A remission was obtained in 17 of the 28 cases. The likelihood of a remission was greater if: (1) the patient was older (mean age was 25.6 years in case of success and 16.6 Years in case of failure); (2) initial daily needs for insulin were smaller (0.88 v. 1.23 U/kg); and (3) stimulated secretion of C peptide was larger (0.22 v. 0.11 mmol/l).
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PMID:[Remission induced at the early stage of insulin-dependent diabetes: do predictive factors exist?]. 639 May 93

The mechanisms by which the beta cells of pancreatic islets are destroyed in insulin-dependent diabetes mellitus (IDDM) are poorly understood. In this report the pancreatic histo- and immunopathology of two children, both HLA-DR 3/4, DQ 2/8 positive and who both died from cerebral oedema within a day of clinical diagnosis of IDDM, were investigated. Patient 1, a 14-month-old girl, had a 4-week history of polydipsia and polyuria. Patient 2, a 3-year-old boy, had 2 days of illness. Both patients had a similarly severe loss of insulin cells but differed markedly as to the extent of lymphocytic islet infiltration (insulitis). Apart from insulitis, marked islet macrophage infiltration was demonstrated in both patients with the HAM-56 monoclonal antibody. Neither patient showed aberrant expression of HLA class II antigens on insulin-immunoreactive cells, but allele-specific HLA-DQ8 expression was evident on endothelial cells. Glutamic acid decarboxylase immunoreactivity was detected in both insulin- and glucagon-immunoreactive cells. It is concluded that the heterogeneity of islet pathology, especially insulitis, may reflect different dynamics and extent rather than different pathomechanisms of immune destruction of islets in IDDM.
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PMID:Heterogeneity of islet pathology in two infants with recent onset diabetes mellitus. 769 19

We report the case of a 62-year-old woman who was admitted to our hospital with diabetic ketoacidosis. Her urinary C-peptide was 3.5 micrograms/day, HLA typing was DR9, and serum was positive for islet cell antibodies. There was no significant increase in the major viral titer. Pancreatic head tumor was suspected, and pancreaticoduodenectomy was performed. The pathology of this tumor was polycystic adenoma. We examined the surgical specimen from around the tumor histologically. The pancreatic islets had decreased in number. The immunohistochemical staining of islets for insulin, glucagon and somatostatin showed that the number of B cells had decreased remarkably, while A and D cells were preserved. Marked lymphocytic infiltration was observed in the islets. The majority of lymphocytes were helper/inducer and suppressor/cytotoxic T cells, which did not express HLA-DR antigen or interleukin-2 receptor. No NK cells were present in the islets. The present case, which was examined histologically in detail, is consistent with the previously proposed hypothesis that autoimmunity might play an important role in the pathogenesis of insulin-dependent diabetes mellitus.
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PMID:Type 1 (insulin-dependent) diabetic patient with remarkable infiltration of lymphocytes to the islets. 795 31

From the present review it appears that insulin-dependent diabetes is a common finding in chronic pancreatitis, and impaired secretion of insulin from beta-cells of the pancreatic islets is essential for the development of this form of secondary diabetes. Judged from a positive correlation between insulin secretory capacity and stimulated pancreatic enzyme output, beta-cell function may decrease in parallel with exocrine pancreatic function. However, in patients with insulin-dependent diabetes secondary to chronic pancreatitis beta-cell function was preserved to a greater extent and glucoregulation was better than in comparable Type 1 (insulin-dependent) diabetic patients. Immunological phenomena and associations with certain HLA-alleles characterizing Type 1 diabetes mellitus were not found in insulin-dependent diabetes secondary to chronic pancreatitis. This may contribute to the slower destruction of the beta-cells in chronic pancreatitis than encountered in Type 1 diabetes. The small number of chronic pancreatitis patients who developed totally absence of endogenous insulin production still have some alpha-cell function during i.v. arginine and meal stimulation. However, insulin-induced hypoglycemia and insulin withdrawal did not stimulate glucagon secretion in the secondary diabetic patients in contrast to comparable Type 1 diabetics. Nevertheless, blood glucose counterregulation is intact in the secondary diabetics due to preserved catecholamine secretion. Furthermore, ketonemia develops during dissipation of insulin, in spite of absence of increased glucagon secretion, emphasizing the role of insulin dissipation for the development of ketoacidosis in this form of diabetes. The suggested increased susceptibility to severe hypoglycemia and less tendency to development of ketonemia may further be influenced by altered insulin sensitivity, nutritional factors and concomitant hepatic failure in diabetes secondary to chronic pancreatitis. Pancreatic polypeptide secretion was absent in chronic pancreatitis without endogenous insulin production. Pancreatic polypeptide secreting cells thus seem to be at least as vulnerable as the beta-cells to the destructive processes characterizing chronic pancreatitis, whereas glucagon secreting alpha-cells preserve secretory capacity to a greater extent than PP-cells and beta-cells. No data, however, favour the view that absent pancreatic polypeptide secretion has any major effect on the glucoregulation in diabetes secondary to chronic pancreatitis. Increased plasma concentration of somatostatin was found in patients with insulin-dependent diabetes secondary to chronic pancreatitis. The source of somatostatin in the patients is unknown, but somatostatin may contribute to a reduction in overall blood glucose level in patients without endogenous insulin secretion due to inhibition of glucagon secretion.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Diabetes mellitus secondary to chronic pancreatitis. 849 94


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