References of "Diabetes"
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See detailHeterozygous inactivation of the Na/Ca exchanger increases glucose-induced insulin release, β-cell proliferation, and mass.
Nguidjoe, E.; Sokolow, S.; Bigabwa, S. et al

in Diabetes (2011), 60

We have previously shown that overexpression of the Na-Ca exchanger (NCX1), a protein responsible for Ca(2+) extrusion from cells, increases β-cell programmed cell death (apoptosis) and reduces β-cell ... [more ▼]

We have previously shown that overexpression of the Na-Ca exchanger (NCX1), a protein responsible for Ca(2+) extrusion from cells, increases β-cell programmed cell death (apoptosis) and reduces β-cell proliferation. To further characterize the role of NCX1 in β-cells under in vivo conditions, we developed and characterized mice deficient for NCX1. RESEARCH DESIGN AND METHODS: Biologic and morphologic methods (Ca(2+) imaging, Ca(2+) uptake, glucose metabolism, insulin release, and point counting morphometry) were used to assess β-cell function in vitro. Blood glucose and insulin levels were measured to assess glucose metabolism and insulin sensitivity in vivo. Islets were transplanted under the kidney capsule to assess their performance to revert diabetes in alloxan-diabetic mice. RESULTS: Heterozygous inactivation of Ncx1 in mice induced an increase in glucose-induced insulin release, with a major enhancement of its first and second phase. This was paralleled by an increase in β-cell proliferation and mass. The mutation also increased β-cell insulin content, proinsulin immunostaining, glucose-induced Ca(2+) uptake, and β-cell resistance to hypoxia. In addition, Ncx1(+/-) islets showed a two- to four-times higher rate of diabetes cure than Ncx1(+/+) islets when transplanted into diabetic animals. CONCLUSIONS: Downregulation of the Na/Ca exchanger leads to an increase in β-cell function, proliferation, mass, and resistance to physiologic stress, namely to various changes in β-cell function that are opposite to the major abnormalities seen in type 2 diabetes. This provides a unique model for the prevention and treatment of β-cell dysfunction in type 2 diabetes and after islet transplantation. [less ▲]

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See detailModulation of the renal response to ACE inhibition by ACE insertion/deletion polymorphism during hyperglycemia in normotensive, normoalbuminuric type 1 diabetic patients
Weekers, Laurent ULg; Bouhanick, B.; Hadjadj, S. et al

in Diabetes (2005), 54(10), 2961-2967

ACE inhibition protects kidney function, but ACE insertion/ deletion (LID) polymorphism affects renal prognosis in type 1 diabetic patients'. ACE genotype may influence the renal benefits of ACE ... [more ▼]

ACE inhibition protects kidney function, but ACE insertion/ deletion (LID) polymorphism affects renal prognosis in type 1 diabetic patients'. ACE genotype may influence the renal benefits of ACE inhibition. We studied the impact of ACE 1/D polymorphism on the renal hemodynamic changes induced by ACE inhibition in type 1 diabetes. We studied renal hemodynamics (glomerular filtration rate [GFR], effective renal plasma flow [ERPF], filtration fraction [GFR/ERPF], mean arterial pressure [MAP], and total renal resistances [MAP/ ERPF]) repeatedly during normoglycemia, and then hyperglycemia in 12 normotensive, normoalbuminuric type 1 diabetes and the 11 genotype (associated with nephrorotection) versus 22 age- and sex-matched subjects with the ACE D allele after three randomly allocated 2- to 6-week periods on placebo, 1.25 mg/day ramipril, and 5.mg/day ramipril in A double-blind, cross-over study. During normoglycemia, the hemodynamic changes induced by ramipril were similar in both genotypes. During hyperglycemia, the changes induced by ramipril were accentuated in the 11 genotype group and attenuated dose dependently in the D allele group (treatment-genotype interaction P values for ERPF, 0.018; MAP 0.018; and total renal resistances, 0.0.55). These results provide a basis to. different renal responses to ACE inbibition according to ACE genotype in type 1 diabetes. [less ▲]

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See detailPolymorphisms in Type-II SH2 domain-containing Inositol 5-Phosphatase (INPPL1, SHIP2) are Associated with Physiological Abnormalities of the Metabolic Syndrome
Kaisaki, P. J.; Delépine, M.; Woon, P. Y. et al

in Diabetes (2004), 53

Type II SH2 domain-containing inositol 5-phosphatase (INPPL1, or SHIP2) plays an important role in the control of insulin sensitivity. INPPL1 mutations affecting gene function have been found in rat ... [more ▼]

Type II SH2 domain-containing inositol 5-phosphatase (INPPL1, or SHIP2) plays an important role in the control of insulin sensitivity. INPPL1 mutations affecting gene function have been found in rat models of type 2 diabetes and hypertension and in type 2 diabetic patients. We investigated the influence of nucleotide variation in INPPL1 on components of the metabolic syndrome. Following comprehensive resequencing of the gene, we genotyped 12 informative polymorphisms in 1,304 individuals from 424 British type 2 diabetes families that were characterized for several metabolic phenotypes. We have found highly significant associations of single nucleotide polymorphisms (SNPs) and haplotypes of INPPL1 with hypertension as well as with other components of the metabolic syndrome. In a cohort of 905 French type 2 diabetic patients, we found evidence of association of INPPL1 SNPs with the presence of hypertension. We conclude that INPPL1 variants may impact susceptibility to disease and/or to subphenotypes involved in the metabolic syndrome in some diabetic patients [less ▲]

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See detailModulation of adipose tissue expression of murine matrix metalloproteinases and their tissue inhibitors with obesity
Maquoi, Erik ULg; Munaut, Carine ULg; Colige, Alain ULg et al

in Diabetes (2002), 51(4), 1093-1101

The potential role of the matrix metalloproteinase (MMP) system in the pathophysiology of the adipose tissue was investigated in a mouse model of nutritionally induced obesity. mRNA levels of 16 MMPs and ... [more ▼]

The potential role of the matrix metalloproteinase (MMP) system in the pathophysiology of the adipose tissue was investigated in a mouse model of nutritionally induced obesity. mRNA levels of 16 MMPs and 4 tissue inhibitors of MMPs (TIMPs) were measured by semiquantitative RT-PCR in adipose tissue isolated from mice maintained for 15 weeks on a standard or high-fat diet. In mice on standard diet, with the exception of MMP-8, all MMP and TIMP transcripts were detected in both gonadal and subcutaneous depots. In obese mice, the expression of MMP-3, -11, -12, -13, and -14 and TIMP-1 mRNAs was upregulated, whereas that of MMP-7, -9, -16, and -24 and TIMP-4 was downregulated. Most MMP and TIMP mRNAs were expressed at higher levels in stromal-vascular cells than in mature adipocytes. Analysis of adipose tissue by in situ fluorescent zymography revealed MMP-dependent proteolytic activities, demonstrating the presence of active MMPs in the intact tissue. In vitro conversion of adipogenic 3T3-F442A cells into mature adipocytes was associated with substantial modulations of MMP and TIMP expression. Moreover, this in vitro adipogenesis was reduced in the presence of a synthetic MMP inhibitor. Thus, the adipose tissue expresses a large array of MMPs and TIMPs, which modulate adipocyte differentiation. [less ▲]

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See detailThe novel diazoxide analog 3-isopropylamino-7-methoxy-4H-1,2,4-benzothiadiazine 1,1-dioxide is a selective Kir6.2/SUR1 channel opener
Dabrowski, M.; Ashcroft, F. M.; Ashfield, R. et al

in Diabetes (2002), 51

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See detailThe gene INPPL1, encoding the lipid phosphatase SHIP2, is a candidate for type 2 diabetes in rat and man
Marion, Evelyne; Kaisaki, Pamela Jane; Pouillon, Valérie et al

in Diabetes (2002), 51

Genetic susceptibility to type 2 diabetes involves many genes, most of which are still unknown. The lipid phosphatase SHIP2 is a potent negative regulator of insulin signaling and sensitivity in vivo and ... [more ▼]

Genetic susceptibility to type 2 diabetes involves many genes, most of which are still unknown. The lipid phosphatase SHIP2 is a potent negative regulator of insulin signaling and sensitivity in vivo and is thus a good candidate gene. Here we report the presence of SHIP2 gene mutations associated with type 2 diabetes in rats and humans. The R1142C mutation specifically identified in Goto-Kakizaki (GK) and spontaneously hypertensive rat strains disrupts a potential class II ligand for Src homology (SH)-3 domain and slightly impairs insulin signaling in cell culture. In humans, a deletion identified in the SHIP2 3' untranslated region (UTR) of type 2 diabetic subjects includes a motif implicated in the control of protein synthesis. In cell culture, the deletion results in reporter messenger RNA and protein overexpression. Finally, genotyping of a cohort of type 2 diabetic and control subjects showed a significant association between the deletion and type 2 diabetes. Altogether, our results show that mutations in the SHIP2 gene contribute to the genetic susceptibility to type 2 diabetes in rats and humans [less ▲]

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See detailRelationship between incipiens nephropathy and cardiac autonomic neuropathy in type 1 diabetes
Estrella, Frederico; Scheen, André ULg; Marchand, Monique et al

in Diabetes (2000), 49(sup. 1), 379-380

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See detailEffects of regular or lispro insulin on glucose metabolism after an oral glucose load in patients with type 2 diabetes mellitus
PAQUOT, Nicolas ULg; Schneiter, Ph; Ruiz, J. et al

in Diabetes (1998), 47(suppl 1), 3

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See detailNeutralization of TNF-a in obese insulin-resistant human subjects: no effect on insulin sensitivity
SCHEEN, André ULg; Castillo, M.; PAQUOT, Nicolas ULg et al

in Diabetes (1996), 45(suppl 2), 286

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See detailHepatic glucose metabolism after fructose ingestion in NIDDM and obses non diabetic subjects.
PAQUOT, Nicolas ULg; Tappy, L.; Schneiter, Ph et al

in Diabetes (1995), 44(suppl 1), 254

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See detailEffects of glucagon on fructose-induced alterations of glucose metabolism in man.
Tappy, L.; Schneiter, Ph; PAQUOT, Nicolas ULg et al

in Diabetes (1994), 44(suppl 1), 254

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See detailGreater efficacy of pulsatile insulin in type I diabetics critically depends on plasma glucagon levels.
Paolisso, G.; Sgambato, S.; Passariello, N. et al

in Diabetes (1987), 36(5), 566-70

The aim of this study was to investigate the role of plasma glucagon levels on the blood glucose response to intravenous insulin administered continuously or in a pulsatile manner. Six type I diabetic ... [more ▼]

The aim of this study was to investigate the role of plasma glucagon levels on the blood glucose response to intravenous insulin administered continuously or in a pulsatile manner. Six type I diabetic patients proven to have no residual insulin secretion were investigated. Endogenous glucagon secretion was inhibited by a continuous intravenous infusion of somatostatin (100 micrograms/h) and replaced by exogenous infusions of the hormone at three different rates (7.5, 4.5, and 2.5 micrograms/h), resulting in three different plasma glucagon steady-state levels (i.e., approximately equal to 200, approximately equal to 130, and approximately equal to 75 pg/ml, respectively). Each subject, in random order and on different days, was infused intravenously with regular human insulin either continuously (0.17 mU X kg-1 X min-1) or with the same amount of insulin infused in a pulsatile manner (0.85 mU X kg-1 X min-1 during 2 min followed by 8 min during which no insulin was infused). At plasma glucagon levels approximately equal to 200 pg/ml, blood glucose rose from approximately 10 to approximately 13 mM without any difference between the two modalities of insulin infusion. For plasma glucagon levels approximately equal to 130 pg/ml, plasma glucose remained steady throughout the experiments, but during the last 40 min, plasma glucose levels were significantly lower when insulin was administered intermittently. This greater blood glucose-lowering effect of pulsatile insulin occurred earlier and was more pronounced for plasma glucagon levels averaging 75 pg/ml. We conclude that the greater hypoglycemic effect of insulin administered intravenously in a pulsatile manner in type I diabetics critically depends on plasma glucagon circulating levels. [less ▲]

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