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

Acetic acid (AcOH), which is a short-chain fatty acid, is reported to have some beneficial effects on metabolism. To test the hypothesis that feeding of AcOH exerts beneficial effects on glucose homeostasis in type 2 diabetes, we fed either a standard diet or one containing 0.3% AcOH to KK-A(y) mice for 8 weeks. Fasting plasma glucose and HbA1c levels were lower in mice fed AcOH for 8 weeks than in control mice. AcOH also reduced the expression of genes involved in gluconeogenesis and lipogenesis, which is in part regulated by 5'-AMP-activated protein kinase (AMPK) in the liver. Finally, sodium acetate, in the form of neutralized AcOH, directly activated AMPK and lowered the expression of genes such as for glucose-6-phosphatase and sterol regulatory element binding protein-1 in rat hepatocytes. These results indicate that the hypoglycemic effect of AcOH might be due to activation of AMPK in the liver.
 ...
PMID:Acetic acid activates hepatic AMPK and reduces hyperglycemia in diabetic KK-A(y) mice. 1663 May 52

The anti-diabetic efficacy of Du-zhong (Eucommia ulmoides Oliver) leaves water extract (WDZ) was investigated in type 2 diabetic animals. The WDZ was given to C57BL/KsJ-db/db mice as a dietary supplement based on 1% dried whole Du-zhong leaves (0.187 g WDZ/100 g standard diet) for 6 weeks. The WDZ supplementation significantly lowered the blood glucose level and enhanced the glucose disposal in an intraperitoneal glucose tolerance test. The plasma insulin and C-peptide levels were significantly higher in the WDZ group than in the control group, while the glucagon level was lower. The hepatic glucokinase activity was significantly higher in the WDZ group, whereas, the glucose-6-phosphatase and phosphoenolpyruvate carboxykinase activities were significantly lower. The WDZ supplementation also significantly lowered the hepatic fatty acid synthase, HMG-CoA reductase and ACAT activities compared to the control group, while it elevated the lipoprotein lipase activity in the skeletal muscle. The WDZ also altered the plasma and hepatic lipid levels by lowering the cholesterol and triglyceride concentrations, while elevating the plasma HDL-cholesterol level. Therefore, these results suggest that WDZ may partly ameliorate hyperglycemia and hyperlipidemia with type 2 diabetes through increasing glycolysis, suppressing gluconeogenesis and the biosynthesis of fatty acid and cholesterol in the liver.
 ...
PMID:Hypoglycemic and hypolipidemic action of Du-zhong (Eucommia ulmoides Oliver) leaves water extract in C57BL/KsJ-db/db mice. 1668 93

Insulin action in the central nervous system regulates energy homeostasis and glucose metabolism. To define the insulin-responsive neurons that mediate these effects, we generated mice with selective inactivation of the insulin receptor (IR) in either pro-opiomelanocortin (POMC)- or agouti-related peptide (AgRP)-expressing neurons of the arcuate nucleus of the hypothalamus. While neither POMC- nor AgRP-restricted IR knockout mice exhibited altered energy homeostasis, insulin failed to normally suppress hepatic glucose production during euglycemic-hyperinsulinemic clamps in AgRP-IR knockout (IR(DeltaAgRP)) mice. These mice also exhibited reduced insulin-stimulated hepatic interleukin-6 expression and increased hepatic expression of glucose-6-phosphatase. These results directly demonstrate that insulin action in POMC and AgRP cells is not required for steady-state regulation of food intake and body weight. However, insulin action specifically in AgRP-expressing neurons does play a critical role in controlling hepatic glucose production and may provide a target for the treatment of insulin resistance in type 2 diabetes.
 ...
PMID:Insulin action in AgRP-expressing neurons is required for suppression of hepatic glucose production. 1755 Jul 79

Type 2 diabetes is characterized by a progressive resistance of peripheral tissues to insulin. Recent data have established the lipid phosphatase SH2 domain-containing inositol phosphatase 2 (SHIP2) as a critical negative regulator of insulin signal transduction. Mutations in the SHIP2 gene are associated with type 2 diabetes. Here, we used hyperglycemic and hyperinsulinemic KKA(y) mice to gain insight into the signaling events and metabolic changes triggered by SHIP2 inhibition in vivo. Liver-specific expression of a dominant-negative SHIP2 mutant in KKA(y) mice increased basal and insulin-stimulated Akt phosphorylation. Protein levels of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase were significantly reduced, and consequently the liver produced less glucose through gluconeogenesis. Furthermore, SHIP2 inhibition improved hepatic glycogen metabolism by modulating the phosphorylation states of glycogen phosphorylase and glycogen synthase, which ultimately increased hepatic glycogen content. Enhanced glucokinase and reduced pyruvate dehydrogenase kinase 4 expression, together with increased plasma triglycerides, indicate improved glycolysis. As a consequence of the insulin-mimetic effects on glycogen metabolism, gluconeogenesis, and glycolysis, the liver-specific inhibition of SHIP2 improved glucose tolerance and markedly reduced prandial blood glucose levels in KKA(y) mice. These results support the attractiveness of a specific inhibition of SHIP2 for the prevention and/or treatment of type 2 diabetes.
 ...
PMID:Normalization of prandial blood glucose and improvement of glucose tolerance by liver-specific inhibition of SH2 domain containing inositol phosphatase 2 (SHIP2) in diabetic KKAy mice: SHIP2 inhibition causes insulin-mimetic effects on glycogen metabolism, gluconeogenesis, and glycolysis. 1759 4

Diabetes and its complications, including oxidative stress, are major reasons for medical intervention and one of the most frequent causes of death in developed countries. Several lines of data suggest that the use of certain dietary polyphenolic compounds may alter glucose metabolism, thus decreasing the risk for type 2 diabetes. In this paper, we present the effect of phenolic acids (caffeic, chlorogenic, rosmarinic, and ferulic) and extracts from Smallanthus sonchifolius and Prunella vulgaris on glucose production in rat hepatocytes and on glucokinase, glucose-6-phosphatase, and phosphoenol-pyruvate carboxykinase mRNA expression in rat hepatoma Fao cells. The phenolics at 500 microM and after 1 h incubation lowered glucose production via both gluconeogenesis (10 mM alanine or dihydroxyacetone as precursors) and glycogenolysis compared with metformin. Most of the phenolics increased the level of glucokinase mRNA after 24 h in the same way as insulin (10(-7) M).
 ...
PMID:Induction of glucokinase mRNA by dietary phenolic compounds in rat liver cells in vitro. 1771 92

The effects of chlorogenic acid (CA) on hepatic glucose output, blood glucose levels and on glucose tolerance were analysed. Hepatic uptake of CA and its effects on hepatic catabolism of L-alanine and glucose-6-phosphatase (G-6-Pase) activity were also evaluated. CA (1 mM) inhibited about 40% of G-6-Pase activity (p < 0.05) in the microsomal fraction of hepatocytes, but no effect was observed on production of glucose from gluconeogenesis or on L-alanine catabolism, at various concentrations of CA (0.33, 0.5 and 1 mM), in liver perfusion experiments. Since there were indications of a lack of uptake of CA by the liver, it is possible that this compound did not reach sufficiently high intracellular levels to inhibit the target enzyme. Accordingly, intravenous administration of CA also failed to provoke a reduction in blood glucose levels. However, CA did promote a significant reduction (p < 0.05) in the plasma glucose peak at 10 and 15 min during the oral glucose tolerance test, probably by attenuating intestinal glucose absorption, suggesting a possible role for it as a glycaemic index lowering agent and highlighting it as a compound of interest for reducing the risk of developing type 2 diabetes.
 ...
PMID:Chlorogenic acid reduces the plasma glucose peak in the oral glucose tolerance test: effects on hepatic glucose release and glycaemia. 1799 Feb 95

SH2-containing inositol 5'-phosphatase 2 (SHIP2) is a 5'-lipid phosphatase hydrolyzing the phosphatidylinositol (PI) 3-kinase product PI(3,4,5)P(3) to PI(3,4)P(2) in the regulation of insulin signaling, and is shown to be increased in peripheral tissues of diabetic C57BL/KSJ-db/db mice. To clarify the impact of SHIP2 in the pathogenesis of insulin resistance with type 2 diabetes, we generated transgenic mice overexpressing SHIP2. The body weight of transgenic mice increased by 5.0% (P < 0.05) compared with control wild-type littermates on a normal chow diet, but not on a high-fat diet. Glucose tolerance and insulin sensitivity were mildly but significantly impaired in the transgenic mice only when maintained on the normal chow diet, as shown by 1.2-fold increase in glucose area under the curve over control levels at 9 months old. Insulin-induced phosphorylation of Akt was decreased in the SHIP2-overexpressing fat, skeletal muscle, and liver. In addition, the expression of hepatic mRNAs for glucose-6-phosphatase and phosphoenolpyruvate carboxykinase was increased, that for sterol regulatory element-binding protein 1 was unchanged, and that for glucokinase was decreased. Consistently, hepatic glycogen content was reduced in the 9-month-old transgenic mice. Structure and insulin content were histologically normal in the pancreatic islets of transgenic mice. These results indicate that increased abundance of SHIP2 in vivo contributes, at least in part, to the impairment of glucose metabolism and insulin sensitivity on a normal chow diet, possibly by attenuating peripheral insulin signaling and by altering hepatic gene expression for glucose homeostasis.
 ...
PMID:Impact of transgenic overexpression of SH2-containing inositol 5'-phosphatase 2 on glucose metabolism and insulin signaling in mice. 1803 90

Diet and nutrition have substantial impact on reducing the incidence of diabetes mellitus, where oxidative stress is an important etiopathological factor. The combined protective role of low dose of naringin (15 mg kg(-1)) and vitamin C (25 mg kg(-1)) and high dose of naringin (30 mg kg(-1)) and vitamin C (50 mg kg(-1)) on streptozotocin (STZ)-induced toxicity was studied in male Wistar rats. To induce type II diabetes mellitus, rats were injected with STZ intraperitoneally at a dose of 45 mg kg(-1) body weight. STZ-induced diabetic rats showed significant increase in blood glucose, water intake, food intake and glycated hemoglobin and significant decrease in plasma insulin, total hemoglobin, body weight and liver glycogen. Diabetic rats also showed significant decrease in the activity of hexokinase and significant increase in the activities of glucose-6-phosphatase and fructose-1,6-bisphosphatase in liver and kidney. The levels of plasma thiobarbituric acid reactive substances, lipid hydroperoxides and vitamin E were elevated while the level of reduced glutathione was decreased in diabetic rats. Glycoprotein components such as hexose, hexosamine, fucose and sialic acid were increased in plasma, liver and kidney of diabetic rats. Oral administration of high doses of naringin (30 mg kg(-1)) and vitamin C (50 mg kg(-1)) to diabetic rats for a period of 21 days normalized all the above-mentioned biochemical parameters. The effect exerted by naringin (30 mg kg(-1)) and vitamin C (50 mg kg(-1)) was similar to the effect exerted by insulin (6 units kg(-1)). Thus, our study shows the antihyperglycemic and antioxidant effects of naringin and vitamin C in STZ-induced type II diabetes mellitus in rats.
 ...
PMID:Combined treatment with naringin and vitamin C ameliorates streptozotocin-induced diabetes in male Wistar rats. 1834 97

Several studies have shown that healthy individuals with fasting plasma glucose (FPG) levels at the high end of the normal range have an increased risk of mortality. To identify genetic determinants that contribute to interindividual variation in FPG, we tested 392,935 single-nucleotide polymorphisms (SNPs) in 654 normoglycemic participants for association with FPG, and we replicated the most strongly associated SNP (rs560887, P = 4 x 10(-7)) in 9353 participants. SNP rs560887 maps to intron 3 of the G6PC2 gene, which encodes glucose-6-phosphatase catalytic subunit-related protein (also known as IGRP), a protein selectively expressed in pancreatic islets. This SNP was associated with FPG (linear regression coefficient beta = -0.06 millimoles per liter per A allele, combined P = 4 x 10(-23)) and with pancreatic beta cell function (Homa-B model, combined P = 3 x 10(-13)) in three populations; however, it was not associated with type 2 diabetes risk. We speculate that G6PC2 regulates FPG by modulating the set point for glucose-stimulated insulin secretion in pancreatic beta cells.
 ...
PMID:A polymorphism within the G6PC2 gene is associated with fasting plasma glucose levels. 1845 Dec 65

Sodium arsenite has been demonstrated to alter the expression of genes associated with glucose homeostasis in tissues involved in the pathogenesis of type 2 diabetes; however, the underlying molecular mechanism has not been fully elucidated yet. In this study, we report that the sodium arsenite-induced gene expression of the small heterodimer partner (SHP; NR0B2), an atypical orphan nuclear receptor, regulates the expression of hepatic gluconeogenic genes. Sodium arsenite augments hepatic SHP mRNA levels in an AMP-activated protein kinase (AMPK)-dependent manner. Sodium arsenite activated AMPK and was shown to perturb cellular ATP levels. The arsenite-induced SHP mRNA level was blocked by adenoviral overexpression of dominant negative AMPK (Ad-dnAMPKalpha) or by the AMPK inhibitor compound C in hepatic cell lines. We demonstrated the dose-dependent induction of SHP mRNA levels by sodium arsenite and repressed the forskolin/dexamethasone-induced gene expression of the key hepatic gluconeogenic genes phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase). Ad-dnAMPKalpha blocked the repressive effects of arsenite-induced SHP on PEPCK and G6Pase. Sodium arsenite inhibited the promoter activity of PEPCK and G6Pase, and this repression was abolished by small interfering (si)RNA SHP treatments. The knockdown of SHP expression by oligonucleotide siRNA SHP or adenoviral siRNA SHP released the sodium arsenite-mediated repression of forskolin/dexamethasone-stimulated PEPCK and G6Pase gene expression in a variety of hepatic cell lines. Results from our study suggest that sodium arsenite induces SHP via AMPK to inhibit the expression of hepatic gluconeogenic genes and also provide us with a novel molecular mechanism of arsenite-mediated regulation of hepatic glucose homeostasis.
 ...
PMID:Sodium arsenite induces orphan nuclear receptor SHP gene expression via AMP-activated protein kinase to inhibit gluconeogenic enzyme gene expression. 1850 31


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>