Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetes may be associated with many genetic disorders. The scientific importance of these often rare disorders resides in the insight they may provide into the possible mechanisms of common diabetes. The type of diabetes varies in these syndromes. Non-insulin-dependent diabetes (NIDDM), clinically similar to common NIDDM, may be found in some syndromes (e.g. Werner's syndrome). In others there may be considerable insulin resistance, such as that present in ataxia telangiectasia. Extreme insulin resistance due to abnormal insulin receptor function is found in the Mendenhall syndrome. The mechanism of diabetes is more obscure in acute intermittent porphyria (AIP), although haem deficiency affecting the cytochrome chain raises interesting possibilities. In glycogen storage disease type I, the diabetes is associated with insulinopenia, following an earlier period in the disease when hypoglycaemia is the rule. IDDM, clinically similar to the common form, is present in the autoimmune polyglandular syndromes. Although a change in the lean:fat ratio is common in many neuromuscular disorders, mechanisms other than insulin resistance would seem to operate. The increased incidence of diabetes in heterozygotes for some of these genetic disorders raises the possibility that many common diabetics are, in fact, heterozygotes for some other disorder. The increased frequency of diabetes in Klinefelter's syndrome, Turner's syndrome and possibly Down's syndrome leads to the hypothesis that non-disjunction may, in some way be associated with the predisposition to diabetes. In several syndromes there is an increased incidence of diabetes in otherwise unaffected relatives of individuals with these syndromes. It is impossible to assess what proportion of common NIDDM or IDDM is made up of heterozygotes for these genetic syndromes.
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PMID:Diabetes secondary to genetic disorders. 144 74

The enzyme glucose-6-phosphatase is critical for maintaining fasting blood sugar levels by increasing hepatic glucose production. Its absence in patients with von Gierke's disease leads to severe hypoglycemia and abnormal accumulation of glycogen (glycogenosis) in the liver. New players that control the expression of glucose-6-phosphatase have been identified that may provide insight into this metabolic disorder, as well as type 2 diabetes.
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PMID:Von Gierke's disease adopts an orphan (and its partner). 1903 40

Hepatocellular carcinoma (HCC) is a common form of cancer that arises from hepatocytes and whose risk may be affected by several known environmental factors, including hepatitis viruses, alcohol, cigarette smoking, and others. Rare monogenic syndromes, such as alpha1-antitrypsin deficiency, glycogen storage disease type I, hemochromatosis, acute intermittent and cutanea tarda porphyria, as well as hereditary tyrosinemia type I are associated with a high risk of HCC. Several common conditions or diseases inherited as polygenic traits e.g. autoimmune hepatitis, type 2 diabetes, a family history of HCC, hypothyroidism, and non-alcoholic steatohepatitis also show an increased risk of HCC compared to the general population. Overall, the genetic susceptibility to HCC is characterized by a genetic heterogeneity; a high individual risk of HCC may thus be caused by several unlinked single gene defects, whose carriers are rare in the general population, or by more common conditions inherited by complex genetics.
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PMID:Risk of HCC: genetic heterogeneity and complex genetics. 2002 54

The liver is an organ with many facets, including a role in energy production and metabolic balance, detoxification and extraordinary capacity of regeneration. Hepatic glucose production plays a crucial role in the maintenance of normal glucose levels in the organism i.e. between 0.7 to 1.1 g/l. The loss of this function leads to a rare genetic metabolic disease named glycogen storage disease type I (GSDI), characterized by severe hypoglycemia during short fasts. On the contrary, type 2 diabetes is characterized by chronic hyperglycemia, partly due to an overproduction of glucose by the liver. Indeed, diabetes is characterized by increased uptake/production of glucose by hepatocytes, leading to the activation of de novo lipogenesis and the development of a non-alcoholic fatty liver disease. In GSDI, the accumulation of glucose-6 phosphate, which cannot be hydrolyzed into glucose, leads to an increase of glycogen stores and the development of hepatic steatosis. Thus, in these pathologies, hepatocytes are subjected to cellular stress mainly induced by glucotoxicity and lipotoxicity. In this review, we have compared hepatic cellular stress induced in type 2 diabetes and GSDI, especially oxidative stress, autophagy deregulation, and ER-stress. In addition, both GSDI and diabetic patients are prone to the development of hepatocellular adenomas (HCA) that occur on a fatty liver in the absence of cirrhosis. These HCA can further acquire malignant traits and transform into hepatocellular carcinoma. This process of tumorigenesis highlights the importance of an optimal metabolic control in both GSDI and diabetic patients in order to prevent, or at least to restrain, tumorigenic activity during disturbed glucose metabolism pathologies.
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PMID:Hepatic stress associated with pathologies characterized by disturbed glucose production. 3122 3

: Cells efficiently adjust their metabolism according to the abundance of nutrients and energy. The ability to switch cellular metabolism between anabolic and catabolic processes is critical for cell growth. Glucose-6 phosphate is the first intermediate of glucose metabolism and plays a central role in the energy metabolism of the liver. It acts as a hub to metabolically connect glycolysis, the pentose phosphate pathway, glycogen synthesis, de novo lipogenesis, and the hexosamine pathway. In this review, we describe the metabolic fate of glucose-6 phosphate in a healthy liver and the metabolic reprogramming occurring in two pathologies characterized by a deregulation of glucose homeostasis, namely type 2 diabetes, which is characterized by fasting hyperglycemia; and glycogen storage disease type I, where patients develop severe hypoglycemia during short fasting periods. In these two conditions, dysfunction of glucose metabolism results in non-alcoholic fatty liver disease, which may possibly lead to the development of hepatic tumors. Moreover, we also emphasize the role of the transcription factor carbohydrate response element-binding protein (ChREBP), known to link glucose and lipid metabolisms. In this regard, comparing these two metabolic diseases is a fruitful approach to better understand the key role of glucose-6 phosphate in liver metabolism in health and disease.
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PMID:Glucose-6 Phosphate, A Central Hub for Liver Carbohydrate Metabolism. 3175 97