scholarly journals Gene Expression Dynamics during Diabetic Periodontitis

2012 ◽  
Vol 91 (12) ◽  
pp. 1160-1165 ◽  
Author(s):  
O.M. Andriankaja ◽  
J. Galicia ◽  
G. Dong ◽  
W. Xiao ◽  
F. Alawi ◽  
...  
Keyword(s):  
Cell Signaling ◽  
Cell Activity ◽  
Gene Clusters ◽  
Mrna Levels ◽  
Tnf Inhibitor ◽  
Periodontal Inflammation ◽  
Gene Expression Dynamics ◽  
Tnf Inhibition ◽  
Type 2 Diabetic

Diabetes impairs the resolution of periodontal inflammation. We explored pathways altered by inflammation in the diabetic periodontium by using ligatures to induce periodontitis in type-2 diabetic Goto-Kakizaki rats. Ligatures were removed after 7 days, and rats were then treated with TNF inhibitor (pegsunercept) or vehicle alone and euthanized 4 days later. RNA was extracted from periodontal tissue, examined by mRNA profiling, and further analyzed by functional criteria. We found that 1,754 genes were significantly up-regulated and 1,243 were down-regulated by pegsunercept (p < 0.05). Functional analysis revealed up-regulation of neuron-associated and retina-associated gene clusters as well as those related to cell activity and signaling. Others were down-regulated by TNF inhibition and included genes associated with host defense, apoptosis, cell signaling and activity, and coagulation/hemostasis/complement. For selected genes, findings with microarray and rt-PCR agreed. PPAR-α was investigated further by immunohistochemistry due to its anti-inflammatory function and was found to be up-regulated in the gingiva during the resolution of periodontal inflammation and suppressed by diabetes. The results indicate that diabetes-enhanced inflammation both up- and down-regulates genes involved in cellular activity and cell signaling, while it predominantly up-regulates genes involved in the host response, apoptosis, and coagulation/homeostasis/complement and down-regulates mRNA levels of neuron, retina, and energy/metabolism-associated genes.

Lack of skeletal muscle uncoupling protein 2 and 3 mRNA induction during fasting in type-2 diabetic subjects

1999 ◽  
Vol 277 (5) ◽  
pp. E830-E837 ◽  
Author(s):  
Hubert Vidal ◽  
Dominique Langin ◽  
Fabrizio Andreelli ◽  
Laurence Millet ◽  
Dominique Larrouy ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Calorie Restriction ◽  
Uncoupling Protein ◽  
Hormone Sensitive Lipase ◽  
Nonesterified Fatty Acid ◽  
Diabetic Patients ◽  
Mrna Levels ◽  
Hormone Sensitive ◽  
Type 2 Diabetic

Skeletal muscle uncoupling protein 2 and 3 (UCP-2 and UCP-3) mRNA levels are increased during calorie restriction in lean and nondiabetic obese subjects. In this work, we have investigated the effect of a 5-day hypocaloric diet (1,045 kJ/day) on UCP-2 and UCP-3 gene expression in the skeletal muscle of type-2 diabetic obese patients. Before the diet, UCP-2 and UCP-3 mRNA levels were more abundant in diabetic than in nondiabetic subjects. The long (UCP-3L) and short (UCP-3S) forms of UCP-3 transcripts were expressed at similar levels in nondiabetic subjects, but UCP-3S transcripts were twofold more abundant than UCP-3Ltranscripts in the muscle of diabetic patients. Calorie restriction induced a two- to threefold increase in UCP-2 and UCP-3 mRNA levels in nondiabetic patients. No change was observed in type-2 diabetic patients. Variations in plasma nonesterified fatty acid level were positively correlated with changes in skeletal muscle UCP-3L( r = 0.6, P < 0.05) and adipose tissue hormone-sensitive lipase ( r = 0.9, P < 0.001) mRNA levels. Lack of increase in plasma nonesterified fatty acid level and in hormone-sensitive lipase upregulation in diabetic patients during the diet strengthens the hypothesis that fatty acids are associated with the upregulation of uncoupling proteins during calorie restriction.

Adiponectin expression in adipose tissue is reduced in first-degree relatives of type 2 diabetic patients

2003 ◽  
Vol 284 (2) ◽  
pp. E443-E448 ◽  
Author(s):  
A. S. Lihn ◽  
T. Østergård ◽  
B. Nyholm ◽  
S. B. Pedersen ◽  
B. Richelsen ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Subcutaneous Adipose Tissue ◽  
Diabetic Patients ◽  
Mrna Levels ◽  
Type 2 Diabetic Patients ◽  
Adiponectin Mrna ◽  
Subcutaneous Adipose ◽  
Type 2 Diabetic

Adiponectin is suggested to be an important mediator of insulin resistance. Therefore, we investigated the association between adiponectin and insulin sensitivity in 22 healthy first-degree relatives (FDR) to type 2 diabetic patients and 13 matched control subjects. Subcutaneous adipose tissue biopsies were taken before and after a hyperinsulinemic euglycemic clamp. FDR subjects were insulin resistant, as indicated by a reduced Mvalue (4.44 vs. 6.09 mg · kg−1· min−1, P < 0.05). Adiponectin mRNA expression was 45% lower in adipose tissue from FDR compared with controls ( P < 0.01), whereas serum adiponectin was similar in the two groups (6.4 vs. 6.6 μg/ml, not significant). Insulin infusion reduced circulating levels of adiponectin moderately (11–13%) but significantly in both groups ( P < 0.05). In the control group, adiponectin mRNA levels were negatively correlated with fasting insulin ( P < 0.05) and positively correlated with insulin sensitivity ( P < 0.05). In contrast, these associations were not found in the FDR group. In conclusion, FDR have reduced adiponectin mRNA in subcutaneous adipose tissue but normal levels of circulating adiponectin. Adiponectin mRNA levels are positively correlated with insulin sensitivity in control subjects but not in FDR. These findings indicate dysregulation of adiponectin gene expression in FDR.

Molecular Mechanism Underlying the Antidiabetic Effects of a Siddha Polyherbal Preparation in the Liver of Type 2 Diabetic Adult Male Rats

2012 ◽  
Vol 18 (1) ◽  
pp. 29-42 ◽  
Author(s):  
Venkataraman Balaji ◽  
Jayaraman Selvaraj ◽  
Sampath Sathish ◽  
Chinnaiyan Mayilvanan ◽  
Karundevi Balasubramanian
Keyword(s):  
Insulin Receptor ◽  
Molecular Mechanism ◽  
Diabetic Rats ◽  
Male Rats ◽  
Tinospora Cordifolia ◽  
Syzygium Aromaticum ◽  
Mrna Levels ◽  
Type 2 Diabetic ◽  
Antidiabetic Effects

A siddha polyherbal preparation consisting of 5 medicinal plants, namely, Asparagus racemosus, Emblica officinalis, Salacia oblonga, Syzygium aromaticum, and Tinospora cordifolia, in equal ratio, was formulated to examine the molecular mechanism by which it exhibits antidiabetic effects in the liver of high-fat and fructose-induced type 2 diabetic rats. The polyherbal preparation treated type 2 diabetic rats showed an increase in insulin receptor, Akt, and glucose transporter2 mRNA levels compared with diabetic rats. Insulin receptor, insulin receptor substrate-2, Akt, phosphorylated Akt substrate of 160kDaThreonine642, α-Actinin-4, β-arrestin-2, and glucose transporter2 proteins were also markedly decreased in diabetic rats, whereas the polyherbal preparation treatment significantly improved the expression of these proteins more than that of metformin-treated diabetic rats. The expression pattern of insulin signaling molecules analyzed in the present study signifies the therapeutic efficacy of the siddha polyherbal preparation.

scholarly journals Decreased Expression Of apM1 in Omental and Subcutaneous Adipose Tissue of Humans With Type 2 Diabetes

2000 ◽  
Vol 1 (2) ◽  
pp. 81-88 ◽  
Author(s):  
Michael A. Statnick ◽  
Lisa S. Beavers ◽  
Laura J. Conner ◽  
Helena Corominola ◽  
Dwayne Johnson ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Subcutaneous Adipose Tissue ◽  
Diabetic Patients ◽  
Mrna Levels ◽  
Type 2 Diabetic Patients ◽  
Omental Adipose Tissue ◽  
Subcutaneous Adipose ◽  
Type 2 Diabetic

We have screened a subtracted cDNA library in order to identify differentially expressed genes in omental adipose tissue of human patients with Type 2 diabetes. One clone (#1738) showed a marked reduction in omental adipose tissue from patients with Type 2 diabetes. Sequencing and BLAST analysis revealed clone #1738 was the adipocyte-specific secreted protein gene apM1 (synonyms ACRP30, AdipoQ, GBP28). Consistent with the murine orthologue, apM1 mRNA was expressed in cultured human adipocytes and not in preadipocytes. Using RT-PCR we confirmed that apM1 mRNA levels were significantly reduced in omental adipose tissue of obese patients with Type 2 diabetes compared with lean and obese normoglycemic subjects. Although less pronounced, apM1 mRNA levels were reduced in subcutaneous adipose tissue of Type 2 diabetic patients. Whereas the biological function of apM1 is presently unknown, the tissue specific expression, structural similarities to TNFα and the dysregulated expression observed in obese Type 2 diabetic patients suggest that this factor may play a role in the pathogenesis of insulin resistance and Type 2 diabetes.

scholarly journals Amelioration of renal alterations in obese type 2 diabetic mice by vasohibin-1, a negative feedback regulator of angiogenesis

2011 ◽  
Vol 300 (4) ◽  
pp. F873-F886 ◽  
Author(s):  
Daisuke Saito ◽  
Yohei Maeshima ◽  
Tatsuyo Nasu ◽  
Hiroko Yamasaki ◽  
Katsuyuki Tanabe ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Therapeutic Efficacy ◽  
Transforming Growth Factor ◽  
Angiogenesis Inhibitor ◽  
Therapeutic Effects ◽  
Mrna Levels ◽  
Diabetic Mice ◽  
Protein Levels ◽  
Type 2 Diabetic

The involvement of VEGF-A as well as the therapeutic efficacy of angiogenesis inhibitors in diabetic nephropathy have been reported. We recently reported the therapeutic effects of vasohibin-1 (VASH-1), an endogenous angiogenesis inhibitor, in a type 1 diabetic nephropathy model (Nasu T, Maeshima Y, Kinomura M, Hirokoshi-Kawahara K, Tanabe K, Sugiyama H, Sonoda H, Sato Y, Makino H. Diabetes 58: 2365–2375, 2009). In this study, we investigated the therapeutic efficacy of VASH-1 on renal alterations in obese mice with type 2 diabetes. Diabetic db/db mice received intravenous injections of adenoviral vectors encoding human VASH-1 (AdhVASH-1) and were euthanized 8 wk later. AdhVASH-1 treatment resulted in significant suppression of glomerular hypertrophy, glomerular hyperfiltration, albuminuria, increase in the CD31+ glomerular endothelial area, F4/80+ monocyte/macrophage infiltration, the accumulation of type IV collagen, and mesangial matrix. An increase in the renal levels of VEGF-A, VEGFR-2, transforming growth factor (TGF)-β1, and monocyte chemoattractant protein-1 in diabetic animals was significantly suppressed by AdhVASH-1 (immunoblotting). AdhVASH-1 treatment significantly recovered the loss and altered the distribution patterns of nephrin and zonula occludens (ZO)-1 and suppressed the increase in the number of fibroblast-specific protein-1 (FSP-1+) and desmin+ podocytes in diabetic mice. In vitro, recombinant human VASH-1 (rhVASH-1) dose dependently suppressed the upregulation of VEGF induced by high ambient glucose (25 mM) in cultured mouse podocytes. In addition, rhVASH-1 significantly recovered the mRNA levels of nephrin and the protein levels of ZO-1 and P-cadherin and suppressed the increase in protein levels of desmin, FSP-1, Snail, and Slug in podocytes under high-glucose condition. Taken together, these results suggest the potential use of VASH-1 as a novel therapeutic agent in type 2 diabetic nephropathy mediated via antiangiogenic effects and maintenance of podocyte phenotype in association with antiproteinuric effects.

scholarly journals Altered clock gene expression and vascular smooth muscle diurnal contractile variations in type 2 diabetic db/db mice

2012 ◽  
Vol 302 (3) ◽  
pp. H621-H633 ◽  
Author(s):  
Wen Su ◽  
Zhongwen Xie ◽  
Zhenheng Guo ◽  
Marilyn J. Duncan ◽  
Jenny Lutshumba ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Clock Gene ◽  
Mesenteric Arteries ◽  
Mrna Levels ◽  
Clock Gene Expression ◽  
Pressor Responses ◽  
Related Proteins ◽  
Type 2 Diabetic

This study was designed to determine whether the 24-h rhythms of clock gene expression and vascular smooth muscle (VSM) contractile responses are altered in type 2 diabetic db/db mice. Control and db/db mice were euthanized at 6-h intervals throughout the day. The aorta, mesenteric arteries, heart, kidney, and brain were isolated. Clock and target gene mRNA levels were determined by either real-time PCR or in situ hybridization. Isometric contractions were measured in isolated aortic helical strips, and pressor responses to an intravenous injection of vasoconstrictors were determined in vivo using radiotelemetry. We found that the 24-h mRNA rhythms of the following genes were suppressed in db/db mice compared with control mice: the clock genes period homolog 1/2 ( Per1/2) and cryptochrome 1/2 ( Cry1/2) and their target genes D site albumin promoter-binding protein ( Dbp) and peroxisome proliferator-activated receptor-γ ( Pparg) in the aorta and mesenteric arteries; Dbp in the heart; Per1, nuclear receptor subfamily 1, group D, member 1 ( Rev-erba), and Dbp in the kidney; and Per1 in the suprachiasmatic nucleus. The 24-h contractile variations in response to phenylephrine (α1-agonist), ANG II, and high K+ were significantly altered in the aortas from db/db mice compared with control mice. The diurnal variations of the in vivo pressor responses to phenylephrine and ANG II were lost in db/db mice. Moreover, the 24-h mRNA rhythms of the contraction-related proteins Rho kinase 1/2, PKC-potentiated phosphatase inhibitory protein of 17 kDa, calponin-3, tropomyosin-1/2, and smooth muscle protein 22-α were suppressed in db/db mice compared with control mice. Together, our data demonstrated that the 24-h rhythms of clock gene mRNA, mRNA levels of several contraction-related proteins, and VSM contraction were disrupted in db/db mice, which may contribute to the disruption of their blood pressure circadian rhythm.

scholarly journals Apelin and APJ regulation in adipose tissue and skeletal muscle of type 2 diabetic mice and humans

2010 ◽  
Vol 298 (6) ◽  
pp. E1161-E1169 ◽  
Author(s):  
Cédric Dray ◽  
Cyrille Debard ◽  
Jennifer Jager ◽  
Emmanuel Disse ◽  
Danièle Daviaud ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Receptor Expression ◽  
Diabetic Patients ◽  
Mrna Levels ◽  
Type 2 Diabetic Patients ◽  
Insulin Resistant ◽  
Type 2 Diabetic

Apelin, an adipocyte-secreted factor upregulated by insulin, is increased in adipose tissue (AT) and plasma with obesity. Apelin was recently identified as a new player in the control of glucose homeostasis. However, the regulation of apelin and APJ (apelin receptor) expression in skeletal muscle in relation to insulin resistance or type 2 diabetes is not known. Thus we studied apelin and APJ expression in AT and muscle in different mice models of obesity and in type 2 diabetic patients. In insulin-resistant high-fat (HF)-fed mice, apelin and APJ expression were increased in AT compared with control. This was not the case in AT of highly insulin-resistant db/ db mice. In skeletal muscle, apelin expression was similar in control and HF-fed mice and decreased in db/ db mice. APJ expression was decreased in both HF-fed and db/ db mice. Control subjects and type 2 diabetic patients were subjected to a hyperinsulinemic-euglycemic clamp, and tissues biopsies were obtained before and at the end of the clamp. There was no significant difference in basal apelin and APJ expression in AT and muscle between control and diabetic patients. However, apelin plasma levels were significantly increased in diabetic patients. During the clamp, hyperinsulinemia increased apelin and APJ expression in AT of control but not in diabetic subjects. In muscle, only APJ mRNA levels were increased in control but also in diabetic patients. Taken together, these data show that apelin and APJ expression in mice and humans is regulated in a tissue-dependent manner and according to the severity of insulin resistance.

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