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)

The prevalence of diabetes due to chronic pancreatitis would appear to be increasing. In western countries this is associated with the known increase in alcohol consumption and AIP. Malnutrition may be etiologic in tropical areas. The incidence of diabetes in chronic pancreatitis is dependent on a number of factors. It is more common in alcohol-induced pancreatitis, rarely occurs after the first attack but tends to increase with time and rises markedly in calcific pancreatitis. Abnormal glucose tolerance occurred in 91% of patients with calcific pancreatitis and 70% of patients with noncalific AIP in our follow up of five to 12 years. This stresses the importance of serial regular glucose tolerance tests in these patients (Table I). The insulin-reserve is severely depleted in most patients who do not yet demonstrate abnormal glucose tolerance, indicating that pancreatitis regularly affects the islets and that nearly all patients are potential diabetics. The beta cells appear to respond better to oral glucose, glucagon or secretin than to i.v. glucose suggesting a selective glucose receptor loss or block to hyperglycemia in chronic pancreatitis. The alpha cells seem to be more resistant to the effects of chronic pancreatitis but true hypoglucagonemia was found in 16% of patients. In addition, stimulated growth hormone secretion may be deficient in pancreatic diabetes. These last two factors, among others, may be responsible for the protracted and even fatal hypoglycemia to which some patients with AIP on insulin therapy are liable. The danger of drug-induced hypoglycemia, coupled with the infrequency of vasculopathy, retinopathy and nephropathy in pancreatic diabetes has induced us to keep these patients hyperglycemic and glycosuric rather than in a sugar-free state, as long as symptoms are contained. Recurrent abdominal pain, marked weight loss and associated steatorrhea often raise special problems in the management of the pancreatic diabetic.
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PMID:Clinical and hormonal aspects of pancreatic diabetes. 80 21

Porphobilinogen deaminase (PBGD) haploinsufficiency (acute intermittent porphyria, AIP) is characterized by neurovisceral attacks when hepatic heme synthesis is activated by endogenous or environmental factors including fasting. While the molecular mechanisms underlying the nutritional regulation of hepatic heme synthesis have been described, glucose homeostasis during fasting is poorly understood in porphyria. Our study aimed to analyse glucose homeostasis and hepatic carbohydrate metabolism during fasting in PBGD-deficient mice. To determine the contribution of hepatic PBGD deficiency to carbohydrate metabolism, AIP mice injected with a PBGD-liver gene delivery vector were included. After a 14 h fasting period, serum and liver metabolomics analyses showed that wild-type mice stimulated hepatic glycogen degradation to maintain glucose homeostasis while AIP livers activated gluconeogenesis and ketogenesis due to their inability to use stored glycogen. The serum of fasted AIP mice showed increased concentrations of insulin and reduced glucagon levels. Specific over-expression of the PBGD protein in the liver tended to normalize circulating insulin and glucagon levels, stimulated hepatic glycogen catabolism and blocked ketone body production. Reduced glucose uptake was observed in the primary somatosensorial brain cortex of fasted AIP mice, which could be reversed by PBGD-liver gene delivery. In conclusion, AIP mice showed a different response to fasting as measured by altered carbohydrate metabolism in the liver and modified glucose consumption in the brain cortex. Glucose homeostasis in fasted AIP mice was efficiently normalized after restoration of PBGD gene expression in the liver.
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PMID:Glucose metabolism during fasting is altered in experimental porphobilinogen deaminase deficiency. 2690 9