Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Males and females both express estrogen receptor (ER) in white adipose tissue (WAT), and estrogens appear to play an important role in regulating WAT in females. However, the role of ER in male WAT was unclear. In this review, we describe our work, which used wild type (WT) and ERalpha-knockout (alphaERKO) male and female mice to determine the role of ERalpha in regulating WAT and brown adipose tissue (BAT). There were progressive increases in WAT with advancing age in alphaERKO compared with WT males; weights of various WAT depots in alphaERKO males were increased by more than 100% compared with WT controls during adulthood. Conversely, BAT weight was similar in alphaERKO and WT males at all ages. Adipocyte areas and numbers were also increased in WAT from alphaERKO compared with WT males. Compared with WT controls, alphaERKO females also had increases in WAT. The alphaERKO mice also had insulin resistance and impaired glucose tolerance, similar to humans lacking ERalpha or aromatase. The obesity in alphaERKO males appeared to involve decreased energy expenditure rather than hyperphagia. In summary, ERalpha absence causes adipocyte hyperplasia and hypertrophy in WAT, but not BAT, and is accompanied by insulin resistance and glucose intolerance in both males and females. These results are the first evidence that the estrogen/ERalpha signaling system is critical in female and male WAT deposition, and may have clinical implications.
Mol Cell Endocrinol 2001 Jun 10
PMID:The role of estrogen and estrogen receptor-alpha in male adipose tissue. 1140 4

To investigate the enteroinsular axis (EIA) in equines oral (oGTT) and intravenous (i.v.GTT) glucose tolerance tests (5.6 and 1 mmol glucose/kg BW, respectively) were performed with healthy, normal weight large horses and Shetland ponies. Plasma was analysed for concentrations of glucose, glucose-dependent insulinotropic polypeptide (GIP) and insulin. In all equines plasma GIP concentrations only increased significantly when glucose was administered orally. The insulin glucose ratio (IGR) was significantly higher during the oGTT than during the i.v.GTT in both races. Basal plasma glucose levels were significantly higher in large horses than in ponies in both experiments. During the oGTT maximum glucose values were significantly higher in ponies. Ponies tended to a higher insulin secretion but the IGRs were identical in both races after oral and intravenous glucose administration. One clinically inconspicuous pony showed hyperinsulinaemia and, in case of the oGTT, insulin resistance, glucose intolerance, and GIP hypersecretion. The results of this study indicate the existence of an EIA in equines due to the higher IGRs during the oGTT. Furthermore, the similarity of plasma GIP levels and IGRs in ponies and large horses suggest a comparable activity of the EIA in both races. Regarding the elevated plasma GIP concentrations of the insulin resistant pony the EIA appears to participate in equine hyperinsulinaemia.
Comp Biochem Physiol A Mol Integr Physiol 2001 Jun
PMID:Glucose-dependent insulinotropic polypeptide (GIP) and the enteroinsular axis in equines (Equus caballus). 1142 26

Treatment of patients after organ transplantation with the immunosuppressive drug cyclosporin A (CsA) is often accompanied by impaired glucose tolerance, thus promoting the development of diabetes mellitus. In the present article we show that 2 to 5 microM CsA diminishes glucose-induced insulin secretion of isolated mouse pancreatic islets in vitro by inhibiting glucose-stimulated oscillations of the cytoplasmic free-Ca(2+) concentration [Ca(2+)](c). This effect is not due to an inhibition of calcineurin, which mediates the immunosuppressive effect of CsA, because other calcineurin inhibitors, deltamethrin and tacrolimus, did not affect the oscillations in [Ca(2+)](c) of the B-cells. The CsA-induced decrease in [Ca(2+)](c) to basal values was not caused by a direct inhibition of L-type Ca(2+) channels. CsA is known to be a potent inhibitor of the mitochondrial permeability transition pore (PTP), which we recently suggested to be involved in the regulation of oscillations. Consequently, CsA also inhibited the oscillations of the cell membrane potential, and it is shown that these effects could not be ascribed to cellular ATP depletion. However, the mitochondrial membrane potential Delta Psi was affected by CsA by inhibiting the oscillations in Delta Psi. Interestingly, the observed reduction in [Ca(2+)](c) could be counteracted by the K(+)(ATP) channel blocker tolbutamide, indicating that the stimulus-secretion coupling was interrupted before the closure of K(+)(ATP) channels. It is concluded that CsA alters B-cell function by inhibiting the mitochondrial PTP. This terminates the oscillatory activity that is indispensable for adequate insulin secretion. Thus, CsA acts on different targets to induce the immunosuppressive and the diabetogenic effect.
Mol Pharmacol 2001 Oct
PMID:Diabetogenic effect of cyclosporin A is mediated by interference with mitochondrial function of pancreatic B-cells. 1156 51

Intrauterine growth retardation (IUGR) increases the risk of developing glucose intolerance and cardiovascular disease in adulthood. Fetal exposure to excess glucocorticoids may contribute to IUGR. Despite the importance of glucose supply for fetal growth, studies on glucose transporter expression in IUGR are few. Two glucose transporters, GLUT1 and GLUT3, are expressed in placenta. In rodent placenta, GLUT1 is replaced by GLUT3 during late gestation. We examined placental GLUT protein expression in 21-day pregnant rats administered dexamethasone (DEX) from day 15 of gestation via osmotic minipump (at doses of 100 or 200 microg/kg body wt. per day). A dose-dependent decline in placental and fetal weight occurred in the DEX groups at day 21. Placental GLUT3 protein expression increased dose-dependently in the DEX groups (by 1.3-fold (n.s) and 2.3-fold (P<0.01), respectively). GLUT1 protein expression also increased dose-dependently in the DEX groups (by 1.6-fold (P<0.05) and 1.9-fold (P<0.01), respectively). In the DEX-treated groups, altered GLUT protein expression occurred in the absence of altered peroxisome proliferator-activated receptor-gamma (PPAR-gamma) protein expression in day 21 placenta; however, PPAR-gamma protein expression in day 21 fetal hearts was greatly suppressed. We conclude that increased placental GLUT1 protein expression may reflect an attempt to increase placental or fetal glucose supply to attenuate the effect of excessive exposure to glucocorticoids to diminish fetal growth, whereas suppression of cardiac PPAR-gamma expression during cardiac development may contribute to the increased risk of developing heart disease found in people of below average birthweight.
Mol Cell Endocrinol 2001 Dec 20
PMID:Enhanced placental GLUT1 and GLUT3 expression in dexamethasone-induced fetal growth retardation. 1173

The aim of this study was to test if a beta-cell defect is associated to deterioration of glucose tolerance early during the natural history of the type 2 diabetes mellitus. In 41 overweight women, with macrosomic infants in their antecedent deliveries, measures of insulin response and insulin sensitivity were derived from a short (45 min) iv glucose test. The early (EIR) and the late (LIR) phase insulin responses and the insulin sensitivity index (Si) were calculated. According the response to 75 g oral glucose test the subjects were divided into two groups: Impaired glucose tolerance (IGT; n = 12), and normal glucose tolerance (NGT; n = 29). EIR was reduced in IGT group (14.9 +/- 3.6 vs 37.0 +/- 4.0; p < 0.002). Glucose tolerance during oral glucose tolerance test (OGTT), correlated inversely to EIR (r = -0.45; n = 41; p < 0.01). A strong correlation of EIR to LIR (r = 0.88; n = 41; p < 0.001) but no correlation between glucose tolerance and Si was found.
J Cell Mol Med
PMID:Beta-cell dysfunctions and insulin resistance in subjects with increased risk for type 2 diabetes mellitus. 1206 62

High dosage of fructose induces insulin resistance, glucose intolerance and alterations in plasma lipid profile in normal rats. Recently, it has been shown that these rats also develop oxidative stress, which plays a prominent role in diabetic pathology. We now report the effect of taurine on the susceptibility of the aorta to lipid peroxidation and also on the activities of enzymic and non-enzymic antioxidants in rats fed a high fructose-diet for 4 weeks. Fructose-fed rats were more susceptible to lipid peroxidation as measured by thiobarbituric acid reactivity, and antioxidant status was significantly lower. Taurine supplementation caused a significant reduction in the production of thiobarbituric acid--reactive substances and significant rises in antioxidant enzyme activities. The levels of lipid peroxides, diene conjugates, lipofuscin and hydroperoxides were significantly higher in fructose-fed rats. When these rats received taurine in drinking water, no peroxidative changes were observed. Increased aorta lipid peroxidation could play a role in the pathology associated with fructose-feeding, and taurine reduces the lipid peroxidation by inducing antioxidant enzymes.
J Biochem Mol Biol Biophys 2002 Apr
PMID:Taurine modulates antioxidant potential and controls lipid peroxidation in the aorta of high fructose-fed rats. 1218 69

The insulin sensitizer drug, rosiglitazone, has been shown to have a protective effect on pancreatic islet cell structure and function in animal models of type 2 diabetes. The identification of new molecular targets associated both with islet cell dysfunction and protection is a crucial research goal. In the present study, a proteomics approach has been used to identify such targets. Obese C57Bl/6J lep/lep mice and lean littermates were given the insulin sensitizer drug BRL49653, rosiglitazone. It normalized the impaired glucose tolerance in lep/lep mice but had no significant effect on glucose tolerance in the lean mice. Pancreatic islet polypeptides were arrayed by a two-dimensional gel electrophoresis system that separated more than 2500 individual spots. Three overexpressed and six underexpressed proteins were significant (p < 0.05) between lep/lep and lean mice, and four were modulated significantly (p < 0.05) by the rosiglitazone treatment of the obese mice. The identity of these differentially expressed proteins was made using mass spectrometric analysis and provided evidence that differential expression of actin-binding proteins may be an important aspect of defective islet function. Rosiglitazone increased carboxypeptidase B expression in both lep/lep and normal mice suggesting that this might be an independent effect of rosiglitazone that contributes to improved insulin processing.
Mol Cell Proteomics 2002 Jul
PMID:Effect of rosiglitazone on the differential expression of diabetes-associated proteins in pancreatic islets of C57Bl/6 lep/lep mice. 1223 79

After a short description of normal glucose homeostasis, recent findings in relation to insulin release in three groups with a high risk of future development of type 2 diabetes are described. Hyperglycemic clamps in subjects with impaired glucose tolerance (IGT) clearly indicate that pancreatic beta cell function is decreased, in addition to the decreased insulin sensitivity. In women with former gestational diabetes mellitus (GDM), insulin release is also lower than in controls. In Caucasian first-degree relatives (FDRs) with normal glucose tolerance, various studies have shown that beta cell function is lower than in controls, while on the average insulin sensitivity is normal. This implies that beta cell function is disturbed earlier in subjects at risk of developing diabetes than is often appreciated. In the near future, the genetic studies currently underway will presumably unravel the pathogenesis of disturbances both in insulin secretion and in insulin action, in type 2 diabetes mellitus.
Mol Cell Endocrinol 2002 Nov 29
PMID:Early disturbances in insulin secretion in the development of type 2 diabetes mellitus. 1243 13

About 80% of pancreatic cancer patients have glucose intolerance or frank diabetes. This observation has led to the following two hypotheses: i. pancreatic cancer causes the associated diabetes and ii. the conditions associated with diabetes promote the development of pancreatic cancer. Evidence supporting both hypotheses has been accumulated in previous studies. This article reviews these studies, especially those that have been conducted recently.
Mol Cancer 2003 Jan 06
PMID:The relationship between diabetes and pancreatic cancer. 1255 42

Some mice become obese whereas others remain lean when raised on a high-energy diet. This study examined the levels of neuropeptide Y (NPY), and of Y1, Y2, Y5 and leptin receptor mRNA expression in the hypothalamic arcuate nucleus (Arc) of chronic high-energy diet-induced obese (DIO) and resistant (DR) mice. Forty mice were divided into two groups and fed either a high-fat (HF: 40% of calories from fat, 20% of calories from saturated fat; n=34) or low-fat (LF: 10% of calories from fat, 1% from saturated fat; n=6) diet. After 22 weeks of feeding, visceral fat accumulation was 69% higher in DIO mice compared with DR mice, and the former showed a moderate level of glucose intolerance. In DIO mice, the levels of NPY and leptin receptor mRNA expressions were significantly higher than in LF mice (+32 and +14%, P<0.001 and 0.05 respectively), indicating central leptin resistance, whereas the DR and LF groups did not differ. The level of Y2 receptor mRNA expression was similar between the DIO and LF groups but, importantly, was reduced approximately 20% in DR mice (P<0.005). The level of Y5 receptor mRNA was 36% lower in DR mice than DIO mice (P<0.05). The differences between DIO and DR mice identified by this study may assist in a better understanding of genetic predisposition to an increased fat deposition induced by a chronic high-fat diet. A low level of Y2 and Y5 receptor mRNA expression may contribute to the prevention of chronic high-energy diet-induced obesity in DR mice.
Brain Res Mol Brain Res 2003 Jul 04
PMID:The level of NPY receptor mRNA expression in diet-induced obese and resistant mice. 1282 51


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