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)

In this review, the results of a series of NMR experiments investigating glucose storage and synthesis in NIDDM patients and normal controls have been summarized. These have shown: 1. The deficit in nonoxidative glucose disposal in NIDDM subjects results from a defect in the muscle glycogen synthesis pathway. 2. Reduced activity of glucose transporter/hexokinase step in this pathway accounts for the reduced rate of glycogen synthesis in NIDDM patients. 3. This reduced activity of GT/Hk is a genetic defect present before the clinical onset of disease in prediabetic descendants of diabetic parents. 4. In muscle from normal, healthy subjects the rate of glycogen synthesis is controlled by the glucose transport/hexokinase activity step and not by the activity of the muscle glycogen synthase enzyme. 5. Hepatic gluconeogenesis is responsible for most hepatic glucose production during an overnight fast in both normal and NIDDM subjects, and increases in gluconeogenic flux are responsible for the increased rate of hepatic glucose production in NIDDM subjects. 6. In contrast to human muscle, where glycogenesis ceases at rest, in the liver gluconeogenesis and glycogenolysis are always active. Numerous previous studies were considered prior to embarking in each of these NMR experiments. In the original research articles we published, the earlier studies were discussed in terms of the relevant literature. Here, however, I have chosen to present the NMR data as simply as possible, in the hope of exposing the significance of these studies by disentangling the results from the complexities of NMR methodology.
Mol Med 1996 Sep
PMID:Nuclear magnetic resonance studies of glucose metabolism in non-insulin-dependent diabetes mellitus subjects. 889 70

N-Myristoyltransferase (NMT) catalyses the transfer of myristate from myristoyl-CoA to the NH2-terminal glycine residue of several proteins and are important in signal transduction. STZ-induced diabetes (an animal model for insulin-dependent diabetes mellitus, IDDM) resulted in a 2-fold increase in rat liver NMT activity as compared with control animals. In obese Zucker (fa/fa) rats (an animal model for non-insulin dependent diabetes mellitus, NIDDM) there was a approximately 4.7-fold lower liver particulate NMT activity as compared with the control lean rat livers. Administration of sodium orthovanadate to the diabetic rats normalised liver NMT activity. These results would indicate that the rat liver particulate N-myristoyltransferase activity appears to be inversely proportional to the level of plasma insulin, implicating insulin in the control of N-myristoylation.
Mol Cell Biochem
PMID:In vivo modulation of N-myristoyltransferase activity by orthovanadate. 892 31

In vivo vanadate and vanadyl have been shown to mimic the action of insulin and to be effective treatment for animal models of both Type I and Type II diabetes. The molecular mechanism of action of the vanadium salts on insulin sensitivity remains uncertain, and several potential sites proposed for the insulin-like effects are reviewed. In human trials, insulin sensitivity improved in patients with NIDDM, as well as in some patients with IDDM after two weeks of treatment with sodium metavanadate. This increase in insulin sensitivity was primarily due to an increase in non-oxidative glucose disposal, whereas oxidative glucose disposal and both basal and insulin stimulated suppression of hepatic glucose output (HGP) were unchanged. Clinically, oral vanadate was associated with a small decrease in insulin requirements in IDDM subjects. Of additional benefit, there was a decrease in total cholesterol levels in both IDDM and NIDDM subjects. Furthermore, there was an increase in the basal activities of MAP and S6 kinases to levels similar to the insulin-stimulated levels in controls, but there was little or no further stimulation with insulin was seen. Further understanding of the mechanism of vanadium action may ultimately be useful in the design of drugs that improve glucose tolerance.
Mol Cell Biochem
PMID:In vivo and in vitro studies of vanadate in human and rodent diabetes mellitus. 892 42

The mitochondrial enzyme glycerophosphate dehydrogenase (mGDH) plays an essential role in the B-cell glucose-sensing device and its activity in islet homogenates is impaired in several animal models of type 2 diabetes. We have now developed a polyclonal antibody, raised against a recombinant mGDH fragment product, that could be used for the immunodetection of mGDH. Total RNA was isolated from rat pancreatic islets and used in the synthesis of cDNA. Specific primers were designed that corresponded to the FAD binding domain of mGDH. The PCR product was purified and cloned into an appropriate expression vector used for transformation of Escherichia coli cells. The fusion protein was extracted from the transformed cells, further purified, and used for immunization of rabbits. The antibody recognized a single band of 72 kDa in rat islets and testis. The recombinant mGDH product was also recognized as a single band with the expected 65-kDa reference. An ELISA procedure was designed for detection of antibodies against the recombinant mGDH fragment product. The availability of the mGDH antibody opens the way to a number of further applications such as immunocytochemis- try and mGDH quantification in biological material.
Biochem Mol Med 1996 Dec
PMID:Immunodetection of mitochondrial glycerophosphate dehydrogenase (mGDH) by a polyclonal antibody raised against a recombinant mGDH fragment product. 898 43

Vanadium and its compounds exhibit a wide variety of insulin-like effects. In this review, these effects are discussed with respect to the treatment of type I and type II diabetes in animal models, in vitro actions, antineoplastic role, treatment of IDDM and NIDDM patients, toxicity, and the possible mechanism(s) involved. Newly established CytPTK plays a major role in the bioresponses of vanadium. It has a molecular weight of approximately 53 kDa and is active in the presence of Co2+ rather than Mn2+. Among the protein-tyrosine kinase blockers, staurosporine is found to be a potent inhibitor of CytPTK but a poor inhibitor of InsRTK. Vanadium inhibits PTPase activity, and this in turn enhances the activity of protein tyrosine kinases. Our data show that inhibition of PTPase and protein tyrosine kinase activation has a major role in the therapeutic efficacy of vanadium in treating diabetes mellitus.
Crit Rev Biochem Mol Biol 1996 Dec
PMID:Vanadium salts as insulin substitutes: mechanisms of action, a scientific and therapeutic tool in diabetes mellitus research. 899 1

A mutation in the hepatocyte nuclear factor-4 alpha (HNF-4 alpha) gene has been recently reported to cause maturity-onset diabetes of the young (MODY) (Yamagata, Furuta, et al., 1996). The mutation can also be a good candidate for the responsible gene of non-insulin dependent diabetes mellitus (NIDDM). The existence of the mutated allele of Q268X (C to T substitution within the exon 7 of HNF-4 alpha gene) was searched in 514 alleles of Japanese NIDDM patients by polymerase chain reaction-restriction fragment length polymorphism analysis. No mutation was found in these patients. The result showed that the Q268X mutation of HNF-4 alpha gene was not frequent among general NIDDM patients and that it cannot serve as the major diabetogenic gene in the Japanese ethnic group.
Res Commun Mol Pathol Pharmacol 1996 Dec
PMID:Hepatocyte nuclear factor-4 alpha gene mutations in Japanese non-insulin dependent diabetes mellitus (NIDDM) patients. 902 79

Insulin bindings in the tissues and cells in the skin of non-diabetic (control) and genetically diabetic db/db (NIDDM) mice were investigated by in vivo microradioautography at 3 and 15 min. after intravenous injection of 125I-insulin. Specific insulin bindings were observed in the interfollicular epidermis, infundibulum, dermis, outer root sheath, sebaceous glands and blood vessels, but not in the hair shaft of the control mice. Although the specific bindings were seen in the interfollicular epidermis, infundibulum, outer root sheath and blood vessels in the NIDDM mice, the bindings were much less than those of the control mice at both 3 and 15 min. after 125I-insulin injection with an exception of the blood vessels at 3 min. The possible relationships between NIDDM and acanthosis nigricans from the viewpoint of insulin binding are considered.
Cell Mol Biol (Noisy-le-grand) 1997 Mar
PMID:In vivo microradioautographic study of insulin binding in the skin of normal and NIDDM mice: with special reference to acanthosis nigricans. 913 Jun

Diabetes mellitus associated with mitochondrial tRNA mutation at position 3243(DM-Mt3243) is a new disease. Patients have a distinctly different picture from MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes). During observations at the Saiseikai Central Hospital, the following findings were noted in DM-Mt3243 patients: DM-Mt3243 patients are diagnosed earlier with diabetes, compared to NIDDM (non-insulin dependent diabetes mellitus) controls without family history. DM-Mt3243 patients often need insulin more often than NIDDM controls without family history. Post-treatment neuropathy and insulin edema are often found in DM-Mt3243, and the two phenomena possibly have a similar pathophysiology related to mitochondrial dysfunction. Ambiguous psychiatric disorders of functional psychosis are observed frequently in DM-Mt3243. Mild headache is common in DM-Mt3243 cases. Ambiguous neuromuscular abnormalities such as sleep disturbance, paresthesia of the legs, edema of the legs, and palpitation may be symptoms associated with mitochondrial dysfunction in DM-Mt3243. Coenzyme Q may be effective in the relief of these neuromuscular symptoms.
Mol Aspects Med 1997
PMID:Diabetes mellitus associated with 3243 mitochondrial tRNA(Leu(UUR)) mutation: clinical features and coenzyme Q10 treatment. 926 20

Selected esters of succinic acid are currently under investigation as possible insulinotropic tools in the treatment of non-insulin-dependent diabetes mellitus. Novel esters with high insulinotropic efficiency were recently synthesized. The present study concerns the effects of two of these novel esters, namely glycerol-1,2-dimethylsuccinate (2.5 mM) and propanediol-1,2-dimethylsuccinate (1.0 mM), upon the release of insulin and the de novo biosynthesis of peptides in islets from hereditarily diabetic Goto-Kakizaki rats. Whereas D-glucose (2.8 to 16.7 mM) caused a concentration-related stimulation of insulin release in the islets of the diabetic rats, the two esters of succinic acid only increased modestly, and often not significantly, insulin secretion. Nevertheless, they both markedly increased the incorporation of L-[4-3H]phenylalanine into trichloroacetic acid-precipitable material in islets deprived of any other exogenous nutrient. These findings indicate that, at variance with all pharmaceutical agents presently used or proposed as insulin secretagogues in the treatment of type 2 diabetes, glycerol-1,2-dimethylsuccinate and propanediol-1,2-dimethylsuccinate, considered as islet cell nutrients, display, in addition to their insulinotropic action, the property of stimulating biosynthetic activity in the endocrine pancreas of animals affected by this disease.
Res Commun Mol Pathol Pharmacol 1997 Oct
PMID:Effects of glycerol-1,2-dimethylsuccinate and propanediol-1,2-dimethylsuccinate on insulin release and protein biosynthesis in islets of Goto-Kakizaki rats. 943 19

The mitochondrial enzyme FAD-linked glycerophosphate dehydrogenase (mGDH) plays a key role in the recognition of glucose as a stimulus for insulin release from the pancreatic islet B-cell. In the present study, an ELISA procedure was used for the measurement of mGDH antibodies in both insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetic patients. Positive readings, exceeding the upper limit of the normal range, were recorded in 7 out of 12 IDDM patients, as distinct (P < 0.01) from 2 out of 12 nondiabetic subjects of comparable age. The study conducted in 41 NIDDM patients and 15 control subjects of similar age indicated that the incidence of mGDH-positive cases was not significantly different in the diabetic (4/41) and control (1/15) groups, the measurement of optical density in the positive cases barely exceeding the upper limit of the normal range. These findings indicate that the mitochondrial enzyme mGDH often acts as an antigenic determinant in IDDM, but not in NIDDM, patients.
Biochem Mol Med 1997 Dec
PMID:Enzyme-linked immunosorbent assay of autoantibodies against mitochondrial glycerophosphate dehydrogenase in insulin-dependent and non-insulin-dependent diabetic subjects. 944 69


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