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)

High-dose intravenous insulin infusion at the onset of IDDM has been suggested to improve beta-cell function during the 1st year of insulin treatment. To test this hypothesis, we randomly assigned newly diagnosed IDDM patients to receive either an experimental 2-week high-dose intravenous insulin infusion (n = 9; age, 25 +/- 7 years; HbA1e, 10.5 +/- 2.0%) or an intensive insulin therapy of four injections per day (n = 10; age, 28 +/- 7 years; HbA1c, 12.3 +/- 3.0%). The experimental-therapy group received three times more insulin (1.2 +/- 0.4 U.kg-1.day-1) than the intensive-therapy group (0.4 +/- 0.1 U.kg-1. day-1, P < 0.0005). By week 3, both groups were treated similarly with intensive insulin therapy and were followed for 1 year. beta-cell function was evaluated with fasting plasma C-peptide and glucagon-stimulated and mixed meal-stimulated C-peptide concentrations. In both groups, insulin doses were comparable, and HbA1c levels were near normal during follow-up. At diagnosis of IDDM, fasting C-peptide was 0.40 +/- 0.13 nmol/l in the experimental-therapy group and 0.39 +/- 0.23 nmol/l in the intensive-therapy group. Irrespective of treatment, a slight decline of fasting C-peptide was observed in sequential measurements up to 12 months in both groups (delta, -0.13 and -0.08 nmol/l, respectively; NS). Glucagon-stimulated C-peptide concentrations decreased from 0.54 +/- 0.18 and 0.70 +/- 0.39 nmol/l at month 0 to 0.41 +/- 0.20 and 0.61 +/- 0.52 nmol/l, respectively, at month 12. In the experimental-therapy group, mixed meal-stimulated C-peptide concentrations (area under the curve over 2 h) increased from 82.10 +/- 43.72 to 101.20 +/- 32.53 nmol/l and in the intensive-therapy group, from 75.05 +/- 46.01 to 107.20 +/- 102.51 nmol/l. Changes in stimulated C-peptide concentrations between month 0 and 12 were not significant in both groups. During follow-up, fasting and stimulated C-peptide concentrations were not significantly different between the experimental-therapy group and the intensive-therapy group. We conclude that as initial treatments of newly diagnosed IDDM, high-dose intravenous insulin infusion and intensive insulin therapy equally preserve beta-cell function during the 1st year of insulin therapy.
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PMID:High-dose intravenous insulin infusion versus intensive insulin treatment in newly diagnosed IDDM. 931 57

To determine whether improved metabolic control during the first two years of insulin-dependent diabetes (IDDM) modified beta cell function, we studied 108 subjects with recent-onset IDDM diagnosed between March 1986 and April 1992 and followed up prospectively for 2 years. Two insulin regimens were used: 1) conventional insulin treatment (CIT) (1986-90, n = 67) involving a mixture of regular and intermediate insulin before breakfast and dinner; and 2) intensive insulin treatment (IIT) (1990-92, n = 41) providing regular insulin before breakfast and lunch, and a mixture of regular and long-acting insulin before dinner. Glucagon-stimulated C-peptide was determined at diagnosis and at 3, 6, 12 and 24 months. Both groups had similar clinical, metabolic and immunological characteristics at diagnosis. The IIT group had better metabolic control at any given time-point after diagnosis (mean HbA1 during follow-up in CIT: 9.86 +/- 0.28%; IIT: 8.18 +/- 0.04%; p < 0.001) (normal < 9.0%). C-peptide was increased in the IIT group 3 and 6 months after diagnosis (month 0: 0.36 +/- 0.05 nmol/l; month 6: 0.55 +/- 0.06 nmol/l; p < 0.006), but not in the CIT group (month 0: 0.39 +/- 0.04 nmol/l; month 6: 0.45 +/- 0.04 nmol/l; p = NS). Two years after diagnosis, the IIT group maintained initial C-peptide secretion (2 years: 0.37 +/- 0.04 nmol/l) whereas C-peptide was reduced in the CIT group (2 years: 0.23 +/- 0.06 nmol/l) compared to the initial value (p < 0.001) or to that of the IIT group (p = 0.017). Thus, sustained improvement in metabolic control with IIT resulted in better beta-cell function during the first two years after IDDM diagnosis.
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PMID:Improved metabolic control preserved beta-cell function two years after diagnosis of insulin-dependent diabetes mellitus. 934 45

To investigate whether recombinant human insulin-like growth factor-I (rhIGF-I) has direct effects on the insulin requirement to maintain euglycemia independent of the growth hormone (GH) level, nine subjects with insulin-dependent diabetes mellitus ([IDDM] seven females; median (range) age, duration of diabetes, and hemoglobin A1C [HbA1C], 16.9 (12.5 to 21.9) years, 11.8 (4.6 to 16.8) years, and 9.8% (7.9% to 14.1%), respectively) underwent two euglycemic studies (6:00 PM to 8:00 AM) after double-blind subcutaneous administration of rhIGF-I/placebo (40 microg/kg). Octreotide infusion (300 ng/kg/h) suppressed endogenous GH, and three identical discrete GH pulses were infused on both nights. Variable-rate insulin infusion maintained euglycemia. Samples were taken every 15 minutes (glucose and GH), 30 minutes (insulin and intermediate metabolites), and 60 minutes (IGF-I and nonesterified fatty acids [NEFA]). Variables were analyzed during the steady-state period of euglycemia (4:00 to 8:00 AM). Data are expressed as the mean +/- SEM. The insulin infusion rate and free-insulin level were both significantly reduced after rhIGF-I administration (0.13 +/- 0.03 v placebo 0.23 +/- 0.05 mU/kg/min, P = .04, and 8.4 +/- 1.3 v placebo 12.1 +/- 1.4 mU/L, P = .03, respectively). GH pulse-related changes in the insulin requirement observed after placebo were not present after rhIGF-I. Glucagon levels were equally suppressed on both nights. Insulin clearance was not altered after rhIGF-I administration. NEFA and ketone levels also were not different on the 2 nights. In conclusion, in adolescents and young adults with diabetes, rhIGF-I administration directly affected insulin requirements independent of GH levels, but had no effect on fatty acid or ketone levels. This difference is related to the abolition of changes in the insulin requirement after GH pulses, and would suggest a complex interaction between GH and IGF-I on insulin action.
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PMID:Recombinant human insulin-like growth factor-I abolishes changes in insulin requirements consequent upon growth hormone pulsatility in young adults with type I diabetes mellitus. 944 Apr 74

Proglucagon contains the sequence of two glucagon-like peptides, GLP-1 and GLP-2, secreted from enteroendocrine cells of the small and large intestine. GLP-1 lowers blood glucose in both NIDDM and IDDM patients and may be therapeutically useful for treatment of patients with diabetes. GLP-1 regulates blood glucose via stimulation of glucose-dependent insulin secretion, inhibition of gastric emptying, and inhibition of glucagon secretion. GLP-1 may also regulate glycogen synthesis in adipose tissue and muscle; however, the mechanism for these peripheral effects remains unclear. GLP-1 is produced in the brain, and intracerebroventricular GLP-1 in rodents is a potent inhibitor of food and water intake. The short duration of action of GLP-1 may be accounted for in part by the enzyme dipeptidyl peptidase 4 (DPP-IV), which cleaves GLP-1 at the NH2-terminus; hence GLP-1 analogs or the lizard peptide exendin-4 that are resistant to DPP-IV cleavage may be more potent GLP-1 molecules in vivo. GLP-2 has recently been shown to display intestinal growth factor activity in rodents, raising the possibility that GLP-2 may be therapeutically useful for enhancement of mucosal regeneration in patients with intestinal disease. This review discusses recent advances in our understanding of the biological activity of the glucagon-like peptides.
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PMID:Glucagon-like peptides. 951 8

Islet allografts in insulin-dependent diabetic (IDDM) patients exhibit variable survival lengths and low rates of insulin-independence despite treatment with anti-T-cell antibodies and maintenance immunosuppression. Use of poorly characterized freshly isolated preparations makes it difficult to determine whether failures are caused by variations in donor tissue. This study assesses survival of standardized beta-cell allografts in C-peptide negative IDDM patients on maintenance immunosuppression following kidney transplantation and without receiving anti-T-cell antibodies or additional immunosuppression. Human islets were isolated from pancreatic segments after maximal 20 h cold-preservation. During culture, preparations were selected according to quality control tests and combined with grafts with standardized cell composition (> or = 50% beta cells), viability (> or = 90%), total beta-cell number (1 to 2 x 10(6)/kg body weight) and insulin-producing capacity (2 to 4 nmol x graft(-1) x h(-1)). Grafts were injected in a liver segment through the repermeabilized umbilical vein. After 2 weeks C-peptide positivity, four out of seven recipients became C-peptide negative; two of them were initially GAD65-antibody positive and exhibited a rise in titre during graft destruction. The other three patients remained C-peptide positive for more than 1 year, two of them becoming insulin-independent with near-normal fasting glycaemia and HbA1c; they remained GAD65- and islet cell antibody negative. The three patients with surviving grafts presented a history of anti-thymocyte globulin therapy at kidney transplantation. Long-term surviving grafts increased C-peptide release following intravenous glucagon or oral glucose but not following intravenous glucose. Thus, cultured human beta-cells can survive for more than 1 year in IDDM patients on maintenance anti-rejection therapy for a prior kidney graft and without the need for an increased immunosuppression at the time of implantation. The use of functionally standardized beta-cell grafts helps to identify recipient and graft factors which influence their survival and metabolic effects. Insulin-independence can be achieved by injection of 1.5 million beta-cells per kg body weight in a liver segment. These beta-cell implants respond well to adenylcyclase activators but poorly to glucose.
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PMID:Implantation of standardized beta-cell grafts in a liver segment of IDDM patients: graft and recipients characteristics in two cases of insulin-independence under maintenance immunosuppression for prior kidney graft. 956 50

We report the case of a 49-yr-old man affected by coma and hypoglycemia unawareness following repetitive hypoglycemic episodes due to dumping syndrome. The dumping syndrome, which was due to partial gastrectomy and vagotomy performed for recurrent peptic ulcer, was responsible for reactive hyperinsulinemia as demonstrated by an oral glucose tolerance test. While the glucose counterregulatory hormones were all normally sensitive to specific stimulation tests, insulin-induced hypoglycemia failed to induce an adequate counterregulatory response, causing no response in plasma norepinephrine, a slight and short increase in plasma cortisol, ACTH and glucagon and an insufficient increase in plasma epinephrine and GH. This case demonstrates that hypoglycemia unawareness has to be taken into account not only in patients affected by IDDM or insulinoma but also in any case of reactive hypoglycemia.
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PMID:Hypoglycemia unawareness in a patient with dumping syndrome: report of a case. 976 63

We report a 79-year-old woman case of slowly progressive IDDM (SPIDDM) with rheumatoid arthritis (RA) and Hashimoto disease. High titer of anti-glutamic acid decarboxylase antibody (GAD) with a value of 16,400 U/ml (normal value: less than 5 U/ml) and deteriorated secretion of insulin, and clinical course led to the diagnosis of SPIDDM. Both anti-islet cell and anti-insulin antibodies were negative. One year prior to the diagnosis, at 78 years of age, she was newly diagnosed with NIDDM and had been medicated with sulfonylurea and voglibose, resulting her glucose levels well-controlled. Four months before admission, a gradual increase of plasma glucose was noticed, while oral hypoglycemic agents were fully administrated. On admission, her glycemic control was revealed as follows; a fasting blood glucose level of 458 mg/dl and an HbA1 C level of 14.3%. Urinary CPR was 22.5 micrograms day. Her insulin secretion was proved not to be induced with intravenous glucagon injection. Hyperinsulinemic euglycemic glucose clamp test showed the normal glucose uptake ratio; 9.5 mg/kg/min. Moderate doses of subcutaneous insulin (20 units daily) were effective on her diabetes control. She was newly diagnosed with Hashimoto disease that required thyroid hormone replacement 50 micrograms per day after having developed NIDDM. High titer of anti-thyroglobulin antibody (46.9 U/ml) and anti-thyroid peroxidase antibody (81.5 U/ml) were observed. The patient had been medicated for RA with anti-inflammatory drugs since her early seventieth. Rheumatoid factor was elevated to 127.7 IU/L and, anti-nuclear antibody (x 80) and anti-DNA antibody (x 80) were present. It may be of interest that a specific phenotype of HLA; A24 (9) and DR9 recognized to be susceptible to IDDM was detected in the high-elderly onset SPIDDM. Taken together HLA typing with her history of both RA and Hashimoto disease, our case may provide the information to the mechanism of pathogenesis of SPIDDM. Furthermore, to out knowledge, this is the first case of SPIDDM in the aged; 75-year-old or more.
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PMID:[Slowly progressive IDDM with rheumatoid arthritis and Hashimoto disease in high elderly]. 977 59

Hypoglycaemia is a frequent acute complication of IDDM and is usually defined as a blood glucose level below 3.0 mmol/l. Hypoglycaemia stimulates several neuroendocrine responses, such as secretion of glucagon, adrenaline, growth hormone and cortisol, which are generally increased during this phenomenon. The true prevalence of hypoglycaemia is not known. Studies of the epidemiology of severe hypoglycaemia give prevalences ranging from 2.7 to 85.7 episodes per 100 patients per year. The major risk factor for severe hypoglycaemia is hypoglycaemia unawareness, which occurs particularly in patients with type 1 diabetes of long duration and in those with a history of frequent episodes of hypoglycaemia. The first step in the management of hypoglycaemia is to check blood glucose and to treat hypoglycaemia on the basis of symptoms. Hypoglycaemia requires urgent treatment with a fast-acting carbohydrate or, if severe, with parenteral glucagon or intravenous glucose. Prevention measures should be instituted to prevent subsequent episodes, particularly in younger children with hypoglycaemic seizures or when seizures are recurrent.
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PMID:Hypoglycaemia in children with type 1 diabetes mellitus. 1019 51

This paper summarizes the new classification of diabetes mellitus (and other categories of glucose intolerance) and presents some clinically important aspects of the new insulins. The new classification promises to bring to the field considerable uniformity, previously lacking. The five clinical classes are: Type I (insulin-dependent diabetes mellitus, IDDM), Type II (non-insulin-dependent, NIDDM), "other types", gestational diabetes (GDM) and impaired glucose tolerance (IGT). The two statistical risk classes are: previous abnormality of glucose tolerance (Prev AGT) and potential abnormality of glucose tolerance (Pot AGT). These are mutually exclusive classes. Criteria recommended for use by clinicians and researchers are presented in detail, as well as information on the oral glucose test and normal glucose tolerance. Particular attention is drawn to the differences in glucose metabolism (tolerance) characteristics in non-pregnant adults, children and pregnant females. The new insulins are so called because of increased purity achieved by new purification methods. They are not new formulations or types of insulin. Contamination of insulin preparations by other hormones or compounds (e.g. glucagon, pro-insulin, pancreatic polypeptide) is now at a very low level.
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PMID:Diabetes update. 2128 88


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