Stem cells with the capacity of self-renewal and multilineage differentiation are promising sources for generation of pancreatic cells for cell replacement therapy in diabetes mellitus.Stem cells also show their potential in the studies regarding the embryonic development of several endocrine organs including pancreatic islets,thyroid,parathyroid,and adrenal glands.Moreover,they would be much useful for investigation of pathogenesis and drug screening in endocrine and metabolic diseases.

Metformin has been recommended as the first-line therapy for type 2 diabetes.Besides its ideal glucose-lowering effect,metformin has also been shown to exert beneficial effects on cardiovascular system,including preventing the occurrence and progression of atherosclerosis,reducing risk for cardiovascular events,attenuating myocardial ischemia-reperfusion injury,improving ventricular remodeling,and slowing the progress of heart failure.The activation of adenosine monophosphate activated protein kinase (AMPK) signaling pathway plays a pivotal role in the protective cardiovascular effects resulted from metformin.

[Summary] Glucagon-like peptide-1 ( GLP-1 ) agents play important roles in glycemic control in type 2 diabetes. Moreover, these agents also show various protective effects on cardiovascular system. GLP-1 agents improve vascular endothelial function, ameliorate the risk factors of cardiovascular disease including obesity, hyperglycemia, dyslipidemia and hypertension, delay the occurrence and progression of atherosclerosis, and protect against cardiac ischemia-reperfusion injury and heart failure. Therefore, GLP-1 agents may have beneficial effects on cardiovascular diseases at different stages and in multiple aspects.

Proinsulin is the precursor of mature insulin.Proinsulin to insulin ratio reflects the degree of pancreatic β-cell dysfunction and the progression of type 2 diabetes, and may predict the risk of diabetes development.Some variants in susceptibility genes of diabetes are associated with the elevation of proinsulin to insulin ratio.Moreover, several antidiabetic drugs are able to decrease the proinsulin to insulin ratio in patients with type 2 diabetes.Therefore, the proinsulin to insulin ratio may act as a simple and useful indicator in the etiological study, risk prediction, disease progression and therapeutical evaluation in type 2 diabetes.

Islet β cell protection is one of the key strategies for diabetes treatment. The new antidiabetic drug sodium-glucose cotransporter 2(SGLT2)inhibitor decreases blood glucose by inhibiting glucose reabsorption in the renal tubule, independent of insulin. Various clinical studies have shown that SGLT2 inhibitors improve β cell function. Furthermore, animal experiments have indicated that SGLT2 inhibitors increase β cell mass. SGLT2 inhibitors promote islet regeneration through stimulating β cell proliferation, inhibiting β cell apoptosis and dedifferentiation, enhancing transdifferentiation of α cells to β cells, and initiating progenitor-derived β cell neogenisis. Indirect effects of metabolic improvement(i.e.lowering glucose, losing weight, improving lipid metabolism), inhibiting inflammatory reaction, inducing glucagon-like peptide-1 secreted from α cells, and regulating gene changes might be involved in the β cell protection of SGLT2 inhibitors.

Aged ; Atropine ; Electrocardiography ; Female ; Heart Rate ; drug effects ; Humans ; Male ; Muscarinic Antagonists ; pharmacology ; therapeutic use ; Preoperative Care ; methods ; Quinuclidines ; pharmacology ; therapeutic use

Apoproteins ; analysis ; Epithelium ; chemistry ; ultrastructure ; Humans ; Lung ; chemistry ; pathology ; Nuclear Proteins ; analysis ; Pulmonary Sclerosing Hemangioma ; chemistry ; pathology ; Pulmonary Surfactant-Associated Proteins ; analysis ; Secretory Component ; analysis ; Thyroid Nuclear Factor 1 ; Transcription Factors ; analysis

Objective: To investigate the effect of dimethyl dicarboxylate biphenyl ( DDB) on the proliferation, apoptosis and PPARγ expression of hepatic stellate cells. Methods: HSC-T6 cells were cultured in 96-well plates and 6-well plates, and after the 24-hour drug treatment, the influence of DDB on the proliferation and apoptosis of HSC-T6 were detected respectively by CCK-8 kit and flow cytometry. Quantitative real-time-PCR ( Q-PCR) and Western blotting were adopted to determine the effect of DDB on the PPARγmRNA level and the protein expression in HSC-T6 cells. Results:DDB obviously inhibited the proliferation of HSC-T6 (P<0. 05) and significantly promoted the apoptosis of HSC-T6 (P<0. 05) at the experimental concentration (8-64 μmol·L-1) when compared with the control group (0 μmol·L-1). The expression of PPARγ in drug-treated HSC-T6 was notably improved. Conclusion: DDB can inhibit the proliferation and promote the apoptosis of HSC-T6 cells by up-regulating the expression of PPARγ.

Recent studies have demonstrated an association of glucagon-like peptide-1 (GLP-1) signaling defect with non-alcoholic fatty liver disease (NAFLD).Native GLP-1 and GLP-1-based agents may directly act on hepatocytes through activation of GLP-1 receptors in hepatocytes,resulting in the regulation of gene expression associated with insulin resistance and lipid metabolism,and the suppression of oxidative stress in liver cells.Moreover,GLP-1-based agents have been reported to be effective in improving hepatic endpoints in patients with NAFLD.

BACKGROUND: The elevation of plasma fibrinogen(Fbg) is a key risk factor of cerebrovascular diseases. The evaluation of the monomer polymerization function of fibrin has even more important clinical merit than the detection of Fbg level.OBJECTIVE: To investigate the clinical significance of the monomer polymerization function of fibrin in patients with isehemie cerebrovascular diseases and its impacts on rehabilitative intervention.DESIGN: A case control study employing patients and healthy individual as subjects.SETTING: An Institute of Hematology and Department of Neurology of one university.PARTICIPANTS: Totally 110 patients with different ischemic cerebrovascular disease selected from the Department of Neurology, Union Hospital of Tongji Medical College, Huazhong Science and Technology University from September 2001 to March 2002, and 50 healthy individuals were included in the study.METHODS: Rehabilitative intervention was performed in 31 randomly selected cerebral infarct patients, and the parameters indicating the monomer polymerization functions of fibrin in the plasma were detected by the measurement system for the monomer polymerization function of fibrin.MAIN OUTCOME MEASURES: Abnormal condition of monomer polymerization function of fibrin in each parameter.RESULTS: Each parameter indicating the monomer polymerization functions of fibrin in plasma was significantly increased in ischemic cerebrovascular diseases patients than healthy individuals( P ＜ 0.01 ) . The abnormal rate of Fbg leveland fibrin monomer polymerization velocity (FMPV) was significantly elevated in ischemic cerebrovascular disease patients than healthy individuals ( P ＜ 0. 01 ) . The relative risk(RR) of ischemic cerebrovascular diseases in patients with abnormal FMP functions was 4 to 31 times more than healthy control group. In cerebral infarct group, FMPV of anterior circulation infarct subgroup was significantly elevated than that of posterior circulation infarct and lacunar cerebral infarct subgroups( P ＜ 0.05). The FMP function of anterior cerebral infarct patients was significantly higher than that of healthy group before rehabilitative intervention. Although each FMP parameter reduced after rehabilitative intervention, the difference between was not significant compared with that of before therapy.CONCLUSION: FMP function analysis can completely and objectively reflect the coagulation status of the patients with ischemic cerebrovascular diseases, and it can also reflect the range and severity of infarct to some extent. Although common rehabilitative intervention cannot effectively improve the high-coagulation of the blood, the impacts of specific rehabilitative intervention on the coagulation mechanism deserve further investigation.