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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

D-Glyceraldehyde irreversibly inhibited rat liver glucokinase in a concentration-dependent manner. The inactivation of glucokinase by glyceraldehyde was blocked by the presence of its substrates such as glucose and mannose. Glucokinase was highly sensitive to glyceraldehyde compared with some other glycolytic enzymes (from animal tissues) including hexokinase, glucose-6-phosphate isomerase, 6-phosphofructokinase, glyceraldehyde-3-phosphate dehydrogenase, and pyruvate kinase. The amino acid analysis of untreated and glyceraldehyde-treated glucokinase suggested that glyceraldehyde-induced inactivation of glucokinase is caused by glycation of Lys residues of the enzyme by the triose. Treatment of pancreatic islets with 6 mM glyceraldehyde for 1 h at 37 degrees C caused both inactivation of glucokinase and inhibition of glucose-induced insulin secretion. Another glucose-phosphorylating enzyme (hexokinase) in pancreatic islets, however, was little affected by glyceraldehyde. In addition, glyceraldehyde did not affect the insulin secretory responses of islets to nonglucose secretagogues such as glyceraldehyde and Leu. When pancreatic islets were cultured with a lower concentration (1 mM) of glyceraldehyde for a longer time (17 h) in the presence of 10 mM glucose to mimic the in vivo conditions, both glucokinase activity and glucose-induced insulin secretion were again decreased. This study demonstrates that glucose-induced insulin secretion is impaired by glyceraldehyde through the inactivation of glucokinase. The implication of this finding in the pathophysiology of type II diabetes is discussed.
Diabetes 1993 Jul
PMID:Inhibition of glucose-induced insulin secretion through inactivation of glucokinase by glyceraldehyde. 851 67

In patients with non-insulin-dependent diabetes mellitus (NIDDM) and matched control subjects we examined the interrelationships between in vivo nonoxidative glucose metabolism and glucose oxidation and the muscle activities, as well as the immunoreactive protein and mRNA levels of the rate-limiting enzymes in glycogen synthesis and glycolysis, glycogen synthase (GS) and phosphofructokinase (PFK), respectively. Analysis of biopsies of quadriceps muscle from 19 NIDDM patients and 19 control subjects showed in the basal state a 30% decrease (P < 0.005) in total GS activity and a 38% decrease (P < 0.001) in GS mRNA/microgram DNA in NIDDM patients, whereas the GS protein level was normal. The enzymatic activity and protein and mRNA levels of PFK were all normal in diabetic patients. In subgroups of NIDDM patients and control subjects an insulin-glucose clamp in combination with indirect calorimetry was performed. The rate of insulin-stimulated nonoxidative glucose metabolism was decreased by 47% (P < 0.005) in NIDDM patients, whereas the glucose oxidation rate was normal. The PFK activity, protein level, and mRNA/microgram DNA remained unchanged. The relative activation of GS by glucose-6-phosphate was 33% lower (P < 0.02), whereas GS mRNA/micrograms DNA was 37% lower (P < 0.05) in the diabetic patients after 4 h of hyperinsulinemia. Total GS immunoreactive mass remained normal. In conclusion, qualitative but not quantitative posttranslational abnormalities of the GS protein in muscle determine the reduced insulin-stimulated nonoxidative glucose metabolism in NIDDM.
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PMID:Glycogen synthase and phosphofructokinase protein and mRNA levels in skeletal muscle from insulin-resistant patients with non-insulin-dependent diabetes mellitus. 851 49

Acute effect of streptozotocin-induced diabetes on several parameters of glucose metabolism was investigated in thymus lymphocytes (thymocytes). The cells from diabetics rats accumulated in vitro about 2-fold more fructose 2,6-bisphosphate (Fru-2, 6-P2) in the presence of increasing glucose concentration than cells from normal rats. An increased production of lactate was also observed. Phosphofructokinase-1 (PFK-1) and phosphofructokinase-2 (PFK-2) activities were enhanced in cells from diabetic rats compared with those from normal rats. [U-14C]glucose incorporation into glycogen was also increased in cells from diabetic rats and the 14CO2 liberation was lesser than in cells from normal animals. From these data it may be concluded that the response of thymocytes to streptozotocin-induced diabetes is similar to that observed in other extrahepatic tissues.
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PMID:Streptozotocin-induced diabetes increases fructose 2,6-biphosphate levels and glucose metabolism in thymus lymphocytes. 856 20

A condition similar to insulin-dependent diabetes mellitus (IDDM) was induced in male CD-1 mice by injection of streptozotocin (STZ). Five weeks after treatment, the fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus (SOL) muscles were isolated for analysis. Phosphorous metabolites were quantified by 31P-NMR and HPLC, native myosin was characterized electrophoretically, and activities of metabolic enzymes were measured spectrophotometrically. Relative to control animals, STZ-diabetes resulted in a significant 32% decrease in the FM1 isoform of myosin in EDL and a 24% decrease in IM myosin of SOL. Mass-specific activities of phosphofructokinase, citrate synthase, and cytochrome oxidase were significantly lower in SOL from STZ-diabetic mice than in controls by 23, 18, and 36%, respectively. Intracellular ATP was significantly lower in SOL from STZ-diabetic mice than in controls (3.44 +/- 0.20 mumol g-1 wet weight vs. 4.61 +/- 0.20 mumol g-1, respectively), as was creatine phosphate (11.98 +/- 0.80 mumol g-1 wet weight vs. 14.22 +/- 0.44 mumol g-1). In contrast to results from SOL, there were no significant changes in phosphorus metabolites or enzyme activity in EDL. These results show that the effects of IDDM on levels of phosphorus containing metabolites and maximal activities of key regulatory enzymes in muscle are markedly fiber-type specific. It is suggested that the muscle type-specific effects of STZ-diabetes may be a consequence of differential accumulation of intracellular fatty acids.
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PMID:Responses of mouse fast and slow skeletal muscle to streptozotocin diabetes: myosin isoenzymes and phosphorous metabolites. 859 19

Phosphofructokinase (PFK) is a key rate-limiting enzyme in glycolysis and represents a major control point in the metabolism of glucose. There are at least three known isoforms of PFK in humans, referred to as the muscle, platelet, and liver forms, each of which is differentially expressed in various tissues. The gene for muscle phosphofructokinase, PFKM, is mutated in Tarui disease and conceivably contributes to non-insulin-dependent diabetes mellitus (NIDDM). Based on physical and genetic mapping, we have found that the gene for PFKM does not map to chromosome 1 as previously described, but instead maps to chromosome 12. PCR analysis with a somatic cell hybrid mapping panel using primers derived from intron 6 and exon 18 of the PFKM gene showed consistent amplification of cell lines containing chromosome 12 (concordance, 100%). Fluorescence in situ hybridization analysis with CEPH YAC 762G4, isolated with exon 18 primers, indicated that this clone maps to 12q13, centromeric to the diacylglycerol kinase gene (DAGK) at 12q13. 3. A highly informative genetic marker isolated from YAC 762G4 was used to map PFKM genetically between the CHLC framework markers D12S1090 and D12S390. This placement for 762G4 was significantly proximal to the recently reported locus for a third gene for maturity onset diabetes of the young (MODY). The PFKM-associated microsatellite will be a valuable tool in the evaluation of PFKM in diabetic populations as well as in linkage analysis in families with Tarui disease.
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PMID:Physical and genetic mapping of the muscle phosphofructokinase gene (PFKM): reassignment to human chromosome 12q. 866 Oct 33

The mammalian heart is normally well oxygenated and anaerobic glycolysis is extremely rare except for the production of extra ATP during extreme exercise like a marathon race. Anaerobic glycolysis plays a role when there is a serious impairment in coronary blood flow such as during heart attack and open heart surgery. The control of glycolysis in ischemic myocardial tissue appears to be extremely complex. During aerobic glycolysis, phosphofructokinase is the most important regulatory enzyme that controls the energy requirements of the cell. Under anaerobic conditions, however, glyceraldehyde-3-phosphate dehydrogenase becomes the key enzyme because it responds promptly to any changes in the essential supply of co-factors for oxidation. The conversion of pyruvate to acetyl CoA (aerobic metabolism) involves a series of chain reactions primarily catalyzed by pyruvate dehydrogenase complex which is situated at the cross roads between both aerobic and anaerobic glycolysis. It is important to remember that substrate utilization is carefully controlled by substrate availability. During aerobic metabolism, control mechanisms using fatty acids, lactate and glucose as energy substrates regulate the rate of ATP production according to energy demand. This precise mechanism is upset during ischemia and post-ischemic reperfusion for reasons discussed in this review. The demand for ATP can no longer be met by its supply because of severely reduced anaerobic glycolysis and significantly inhibited beta-oxidation of fatty acids. The impairment of bioenergetics is discussed in the context of several diseases such as cardiomyopathy, heart failure, diabetes, arrhythmias, cardiac surgery, heart-lung transplantation, and also in aging and oxidative stress. The regulation of energy metabolism in preconditioned heart is also discussed. Finally, methods used to preserve energy in ischemic myocardium are summarized and quantitation of the high-energy phosphates is discussed. This review challenges scientists to discover drugs which will stimulate energy supply during myocardial ischemia.
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PMID:Bioenergetics, ischemic contracture and reperfusion injury. 880 94

A quantitative study of the effect of carnitine deficiency on expression of glycolytic and gluconeogenic enzymes was performed using juvenile visceral steatosis mice which are systemically deficient in carnitine. The amounts of glucokinase and L-type pyruvate kinase mRNA were reduced in homozygotes, compared to heterozygotes and normal controls at 2 and 8 weeks. Liver-type phosphofructokinase, however, did not differ significantly. The abundance of fructose 1,6-bisphosphatase mRNA was unchanged at 2 and 8 weeks. The level of phosphoenolpyruvate carboxykinase mRNA was increased slightly at 2 weeks, but not at 8 weeks. A part of these changes could not be explained by the plasma glucose or insulin level. Carnitine administration restored the mRNA of these enzymes to normal levels. These results suggest that carnitine deficiency affects the expression of these liver enzymes.
Diabetes Res Clin Pract 1996 May
PMID:Disordered expression of glycolytic and gluconeogenic liver enzymes of juvenile visceral steatosis mice with systemic carnitine deficiency. 885 99

Crude extracts containing the enzymes obtained from mouse liver were incubated with 3-deoxyglucosone (3-DG), and then subjected to assay of the activities of enzymes responsible for glucose metabolism. Hexokinase and glucose-6-phosphate dehydrogenase activities were decreased by 3-DG and hexokinase activity was strongly inhibited time and concentration dependently, while glucokinase, glucose-6-phosphatase, and phosphofructokinase activities were scarcely affected. These results suggest that 3-DG inhibits the intake of glucose in the liver and a connection with development of diabetes.
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PMID:Effect of 3-deoxyglucosone on the activities of enzymes responsible for glucose metabolism in mouse liver. 887 29

The activity of phosphofructokinase-2, fructose, 1,6-bisphosphatase, glucokinase, and also the level of fructose 2,6-bisphosphate and glycogen were examined in the liver of normal, and streptozotocin-diabetic rats. It was shown that the activity of phosphofructokinase-2 was decreased in the liver of diabetic rats. Besides that the activity determined at pH 6.6 (the "active" or unphosphorylated enzyme form) was 3-fold reduced whereas the "total" enzyme activity as measured at pH 8.5 was lowered 1,7-fold. The phosphofructokinase-2 activity assay at two pH values allows to estimate a degree of phosphorylation of bifunctional enzyme which is markedly enhanced in diabetes. The fall of the bifunctional enzyme k in case activity is accompanied by the lowered fructose 2.6-bisphosphate level, increased fructose 1,6-bisphosphatase activity that in turn favours the liver tissue glycolysis inhibition and gluconeogenesis enhanced in diabetes.
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PMID:[Functional characteristics of fructose-2,6-bisphosphate system in the liver during experimental streptozotocin diabetes]. 913 54

As part of an ongoing search for susceptibility loci for NIDDM, we tested 19 genes whose products are implicated in insulin secretion or action for linkage with NIDDM. Loci included the G-protein-coupled inwardly rectifying potassium channels expressed in beta-cells (KCNJ3 and KCNJ7), glucagon (GCG), glucokinase regulatory protein (GCKR), glucagon-like peptide I receptor (GLP1R), LIM/homeodomain islet-1 (ISL1), caudal-type homeodomain 3 (CDX3), proprotein convertase 2 (PCSK2), cholecystokinin B receptor (CCKBR), hexokinase 1 (HK1), hexokinase 2 (HK2), mitochondrial FAD-glycerophosphate dehydrogenase (GPD2), liver and muscle forms of pyruvate kinase (PKL, PKM), fatty acid-binding protein 2 (FABP2), hepatic phosphofructokinase (PFKL), protein serine/threonine phosphatase 1 beta (PPP1CB), and low-density lipoprotein receptor (LDLR). Additionally, we tested the histidine-rich calcium locus (HRC) on chromosome 19q. All regions were tested for linkage with microsatellite markers in 751 individuals from 172 families with at least two patients with overt NIDDM (according to World Health Organization criteria) in the sibship, using nonparametric methods. These 172 families comprise 352 possible affected sib pairs with overt NIDDM or 621 possible affected sib pairs defined as having a fasting plasma glucose value of >6.1 mmol/l or a glucose value of >7.8 mmol/l 2 h after oral glucose load. No evidence for linkage was found with any of the 19 candidate genes and NIDDM in our population by nonparametric methods, suggesting that those genes are not major contributors to the pathogenesis of NIDDM. However, some evidence for suggestive linkage was found between a more severe form of NIDDM, defined as overt NIDDM diagnosed before 45 years of age, and the CCKBR locus (11p15.4; P = 0.004). Analyses of six additional markers spanning 27 cM on chromosome 11p confirmed the suggestive linkage in this region. Whether an NIDDM susceptibility gene lies on chromosome 11p in our population must be determined by further analyses.
Diabetes 1997 Jun
PMID:Genetics of NIDDM in France: studies with 19 candidate genes in affected sib pairs. 916 80


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