Abstract:
OBJECTIVE:Psammomys obesus gerbil exhibits PKCepsilon over-expression on high-energy (HE) diet. Muscle insulin receptor (IR) signalling and tyrosine kinase activity are inhibited eliciting insulin resistance. We aimed at preventing diabetes by inhibiting PKCepsilon-induced serine phosphorylation of IRS-1 with novel PKCepsilon abrogating peptides. RESEARCH DESIGN:PKCepsilon abrogating peptides were copied from catalytic domain of PKC molecule (PCT patent IL2006/000755). Psammomys fed a diabetogenic HE diet received i.p. peptides KCe-12 and KCe-16 (18 mg/kg) on days 0, 7 and 14 controls received peptide solvent. RESULTS:Food consumption and animal weight remained unchanged. On day 16, non-fasting blood glucose levels returned to normal (90 +/- 5 versus 347 +/- 16 mg/dL in untreated controls). Hyperinsulinemia fell from 584 +/- 55 to 180 +/- 22 mU/L. Western blot analysis showed that the increased phosphoserine(636, 639) content on IRS-1 in gastrocnemius muscle of diabetic animals was reduced three fold, the PKB/AKT activity increased two fold and muscle GLUT4 tended to increase, compared with controls. Likewise, administration of KCe-12 prior to placing the HE diet prevented the onset of diabetes. KCe-12 treatment did not reduce muscle PKCepsilon level. Damage and loss of insulin in pancreatic beta cells on HE diet were prevented by KCe-12, as shown in micrographs of islet hematoxylin-eosin staining and insulin immunostaining. The preserved secretory function enabled Psammomys to normalize glucose homeostasis. CONCLUSIONS:KCe-16 and KCe-12 peptides derived from PKCepsilon substrate-binding region prevented the nutritional diabetes and protected muscle IRS-1 from PKCepsilon-induced serine phosphorylation, abrogating the insulin-signalling impediment in the Psammomys model of type 2 diabetes. Anti-diabetic peptides may lead to novel modalities preventing human overnutrition-induced insulin resistance and diabetes.
journal_name
Diabetes Metab Res Revjournal_title
Diabetes/metabolism research and reviewsauthors
Mack E,Ziv E,Reuveni H,Kalman R,Niv MY,Jörns A,Lenzen S,Shafrir Edoi
10.1002/dmrr.881subject
Has Abstractpub_date
2008-10-01 00:00:00pages
577-84issue
7eissn
1520-7552issn
1520-7560journal_volume
24pub_type
杂志文章abstract:BACKGROUND:While the effect of fatty acids and ectopic triglyceride storage in pancreatic beta cells has been well-defined, only limited information is available on alpha cells. This study evaluates the long-term impact of fatty acids on alpha cell function and proliferation as well as fatty acid oxidation. METHODS:Cl...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章
doi:10.1002/dmrr.663
更新日期:2007-03-01 00:00:00
abstract:BACKGROUND:Malonyl-CoA, an allosteric inhibitor of carnitine palmitoyl transferase, controls the oxidation of fatty acids in muscle and other tissues by regulating their entrance into mitochondria. The level of malonyl-CoA in muscle is influenced by the uptake of energy substrates such as glucose, the precursor of its ...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章
doi:10.1002/dmrr.288
更新日期:2002-05-01 00:00:00
abstract:BACKGROUND:To ascertain which demographic, clinical, and microbiological factors might affect clinical outcomes of patients with diabetic foot infections, excluding known osteomyelitis, by analysing Clinical Assessment Program and Teflaro® Utilization Registry study data of patients treated with ceftaroline fosamil. M...
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pub_type: 杂志文章,多中心研究
doi:10.1002/dmrr.2624
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abstract:BACKGROUND:It has been shown that subjects with normal glucose tolerance (NGT), whose plasma glucose (PG) levels do not return to their fasting PG level within 2 h during an oral glucose tolerance test (OGTT) (Group I), have a significantly higher risk to develop type 2 diabetes than NGT subjects whose 2-h glucose retu...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章
doi:10.1002/dmrr.951
更新日期:2009-05-01 00:00:00
abstract:BACKGROUND:Diabetes mellitus secondary to pancreatic diseases is a condition seldom thought of in clinical practice. Yet, a high percentage of exocrine pancreatic insufficiency has been reported for the general population and especially for diabetic subjects. Thus, we investigated the prevalence of diabetes mellitus du...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章
doi:10.1002/dmrr.2260
更新日期:2012-05-01 00:00:00
abstract:BACKGROUND:Adenosine triphosphate (ATP) is a critical determinant of beta-cell insulin secretion in response to glucose. BHE/cdb rats have a mutation in ATP synthase that limits ATP production, yet develop mild diabetes only with ageing. We investigated the cellular basis for reduced insulin secretion and compensatory ...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章
doi:10.1002/dmrr.819
更新日期:2008-07-01 00:00:00
abstract::Whether diabetic foot ulcerations arise from an amalgam of neuro-ischemic factors or because of arterial occlusive disease alone, the arterial circulation must be thoroughly evaluated. Clinical evaluation is foremost, but numerous non-invasive diagnostic options such as duplex ultrasonography and MRA are often enliste...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章,评审
doi:10.1002/dmrr.468
更新日期:2004-05-01 00:00:00
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journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章,meta分析,评审
doi:10.1002/dmrr.2535
更新日期:2014-10-01 00:00:00
abstract:BACKGROUND:The present study was undertaken to determine whether there were changes evident in axonal membrane function prior to the onset of neuropathy in patients with type 1 and type 2 diabetes. METHODS:From a cohort of 110 consecutive referrals, nerve excitability was investigated in 40 diabetic patients without c...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章
doi:10.1002/dmrr.2360
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journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章
doi:10.1002/dmrr.3310
更新日期:2020-09-01 00:00:00
abstract::Increasing coprevalence of diabetes mellitus (DM) and tuberculosis (TB) in low-income and middle-income countries (LMICs) indicates a rising threat to the decades of progress made against TB and requires global attention. This systematic review provides a summary of type 2 diabetes and tuberculosis coprevalence in var...
journal_title:Diabetes/metabolism research and reviews
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abstract:BACKGROUND:Both metabolic syndrome (MetS) and N-amino terminal fragment of the prohormone B-type natriuretic peptide (NT-proBNP) confer increased risk of cardiovascular diseases (CVD). We assessed if NT-proBNP levels were greater in people with uncomplicated MetS, who had neither CVD/chronic kidney disease (CKD) nor di...
journal_title:Diabetes/metabolism research and reviews
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doi:10.1002/dmrr.2616
更新日期:2015-05-01 00:00:00
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journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章,随机对照试验
doi:10.1002/dmrr.2363
更新日期:2013-01-01 00:00:00
abstract::Fulminant type 1 diabetes (fT1D) is a new subtype of type 1 diabetes proposed by Imagawa in 2000. It is a clinical syndrome characterized by a markedly rapid and almost complete destruction of pancreatic β cells. Metabolic derangement is more severe in this subtype than in autoimmune type 1 diabetes. The incidence of ...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章,评审
doi:10.1002/dmrr.2928
更新日期:2018-01-01 00:00:00
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doi:10.1002/dmrr.2556
更新日期:2014-09-01 00:00:00
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journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章
doi:10.1002/dmrr.2952
更新日期:2018-02-01 00:00:00
abstract::Various different systems have been proposed to classify diabetic foot ulcers, but none has gained widespread acceptance. The International Working Group of the Diabetic Foot (IWGDF) developed a classification system for research purposes, which is described in this report. In this PEDIS system, all foot ulcers should...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章,评审
doi:10.1002/dmrr.464
更新日期:2004-05-01 00:00:00
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journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章,评审
doi:10.1002/1520-7560(200009/10)16:1+<::aid-dmrr130>3.
更新日期:2000-09-01 00:00:00
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journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章
doi:10.1002/dmrr.2992
更新日期:2018-07-01 00:00:00
abstract::Diabetes is an important cause of morbidity and mortality in Africa. Although a dramatic increase in disease burden is projected, it remains to be seen what effect the ongoing devastation of HIV disease will have on the epidemiology of such chronic diseases as diabetes. Recent data on type 2 diabetes prevalence indica...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章,评审
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更新日期:2002-09-01 00:00:00
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pub_type: 杂志文章
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更新日期:2019-11-01 00:00:00
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journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章,评审
doi:10.1002/dmrr.566
更新日期:2005-11-01 00:00:00
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journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章
doi:10.1002/dmrr.963
更新日期:2009-05-01 00:00:00
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journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章,评审
doi:10.1002/dmrr.817
更新日期:2008-05-01 00:00:00
abstract:BACKGROUND:Previous works indicated that the stress on the endoplasmic reticulum (ER) affected nonalcoholic fatty liver disease (NAFLD). However, there is no clear evident on the effect of the regulation of ER stress by angiotensin-converting enzyme 2 (ACE2) on the prevention of NAFLD. METHODS:HepG2 cells were treated...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章
doi:10.1002/dmrr.3123
更新日期:2019-05-01 00:00:00
abstract:BACKGROUND:Although obesity has been associated with a higher risk for premature death, the sex and ethnic-origin specific body mass index (BMI) levels that are associated with increased mortality are controversial. We investigated the 40-year cumulative all-cause mortality, in relation to the BMI in adult life, among ...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章
doi:10.1002/dmrr.2642
更新日期:2015-07-01 00:00:00
abstract::The literature on the role of body iron status in the development of type 2 diabetes (T2D) in humans is inconsistent. We aimed to assess the association between iron indices and T2D by a meta-analysis of previously published studies. A systematic literature search was conducted in PubMed and EMBASE. Observational stud...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章,meta分析,评审
doi:10.1002/dmrr.2506
更新日期:2014-07-01 00:00:00
abstract:BACKGROUND:We evaluated whether global levels of DNA methylation status were associated with retinopathy as well as providing a predictive role of DNA methylation in developing retinopathy in a case-control study of 168 patients with type 2 diabetes. METHODS:The 5-methylcytosine content was assessed by reversed-phase ...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章
doi:10.1002/dmrr.2584
更新日期:2015-02-01 00:00:00
abstract::The exact cause of the obesity epidemic remains unknown; however, both environmental and genetic factors are involved. People at risk of developing obesity include children with type 1 diabetes mellitus (T1DM), which in turn increases their cardiovascular disease risk. Here, we discuss the clinical and genetic factors...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章,评审
doi:10.1002/dmrr.2797
更新日期:2016-10-01 00:00:00
abstract:BACKGROUND:HLA region is the major locus (IDDM1) of type 1 diabetes (T1D) susceptibility. It explains approximately 50% of the genetic background of T1D, indicating additional genetic determinants. Genome scans and candidate gene studies have generated several chromosomal candidate regions that may have a role in T1D d...
journal_title:Diabetes/metabolism research and reviews
pub_type: 临床试验,杂志文章
doi:10.1002/dmrr.424
更新日期:2004-03-01 00:00:00