Postprandial hyperglycemia is one of the characteristics of glucose profiles in Chinese T2DM patients. High-ratio premix insulin analogues with advantages of excellent pharmacokinetic characteristics and flexible and convenient administration provide a comprehensive solution for Chinese T2DM patients to effectively control postprandial glucose and reduce blood glucose fluctuation. This paper is a literature review on its clinical evidence and experience.

A lot of functions of mitofusin 2 have been found,such as promoting mitochondria fusion,inhibiting cell proliferation and protecting cell avoid of apoptosis.Now,more and more evidence suggest that it is involved in insulin resistance.

BACKGROUND:Under certain conditions, stem cel s can be induced to differentiate into vascular endothelial cel s, which can promote the angiogenesis of ischemic lower limbs and the establishment of effective circulation and improve distal blood supply of the ischemic limbs. OBJECTIVE:To review the biological characteristics and pro-angiogenesis mechanism of umbilical cord mesenchymal stem cel s and to investigate the current status of umbilical cord mesenchymal stem cel s in the repair of neuropathy and chronic wounds. METHODS:PubMed, VIP and Wanfang databases were searched for relevant articles published from 2000 to 2015 using the keywords of“stem cel s transplantation, umbilical cord mesenchymal stem cel , diabetic angiopathies”in English and Chinese, respectively. RESULTS AND CONCLUSION:Compared with peripheral blood stem cel s and bone marrow mesenchymal stem cel s, umbilical cord mesenchymal stem cel s are characterized as more widespread sources, easy col ection, stronger amplification ability, no immunogenicity, and no ethical controversy, which have become ideal target and seed cel s for pro-angiogenesis and gene therapy in ischemic diseases. Umbilical cord mesenchymal stem cel s can differentiate into vascular endothelial cel s and fibroblasts involved in wound healing. In addition, these cel s can promote the production and expression of neurotrophic factors, promote nerve regeneration in ischemic tissues, and participate in tissue repair and accelerate healing of ulcers by paracrine and autocrine cytokines, anti-inflammation and immunomodulation. Therefore, umbilical cord mesenchymal stem cel s have a broad prospect in the improvement of diabetic lower limb ischemia, repair of diabetic peripheral neuropathy and promotion of chronic ulcer healing. Compared with stem cel transplantation alone, umbilical cord mesenchymal stem cel s transplantation combined with gene therapy can further enhance cel survival and pro-angiogenesis.

[Summary] Activating transcription factor 4 (ATF4) is an alkaline leucine zipper transcriptional factor ,which is involved in many physiological metabolism processes such as stress response ,inflammation and tumor growth. Moreover ,recent studies have shown that ATF4 also plays a key role in regulating lipid and glucose metabolism ,insulin secretion and insulin sensitivity ,which may related to pathways such as endoplasmic reticulum stress (ERS ) ,peroxisome proliferator‐activated receptor gamma coactivator (PGC1α) and target of rapamycin (TOR). This article summarized the recent research progress of ATF4 in regulating glucose and lipid metabolism.

[Summary] Considerable efforts have been made to understand the cellular and molecular mechanisms of metformin ,a potent antihyperglycemic agent now recommended as the first‐line treatment of patients with T2DM. The main effect of this drug is to reducethe hepatic glucose output ,primarily through inhibition of the mitochondrial respiratory chain complex Ⅰ and then activating AM P‐activated protein kinase (AMPK) ,which provide a generally acceptable mechanism for the action of metformin on hepatic gluconeogenesis. Beyond its effect on glucose metabolism ,metformin has been reported to improve ovarian function of patients with polycystic ovary syndrome (PCOS) and to reduce the risk of microvascular and macrovascular complications in patients with T2DM. In addition ,metfomin has also recently been suggested as an adjuvant treatment of cancer. Here we reviewed the progress of mechanism research and clinical application of metformin.

Objective To study the relationship of free fatty acids and oxLDL-C with diabetic retinopathy(DR).Methods The 108 type 2 diabetes cases with(n=68)and without(n=40)DR were enrolled,and compared with 42 health control.FFA was determined by copper chromogenic method.oxLDL-C was determined by ELISA with kits provided.The correlation of risk factors with retinopathy was analyzed by logistic regression analysis.Results FFA and ox LDL-C levels were higher in DR group than in groups of DM and control.Logistic regression analysis showed that as the independent risk factors for DR pathogenesis,LDL-C,FFA,oxLDL-C and course of disease entered into regression equation.Conclusions FFA and oxLDL-C are the important risk factors for DR.

Objective To observe the effects of high sucrose,high saturated fatty acid and high unsaturated fatty acid(diets) on insulin resistance and endothelium-dependent vasodilation function.Methods Adult Wistar rats were divided into normal control(NC) group,high sucrose(HS) group and high saturated fatty acid(HSF) group,high unsaturated fatty acid(HUF) groups.Insulin sensitivity was tested by hyperinsulinemic-euglucemic clamp after 24 weeks.Acetylcholine-induced(or sodium nitroprussideinduced) relaxation of preconstricted isolated renal arteries was measured by Mulvany myograph.Results GIR was obviously lower in experimental groups than that in NC group.GIR was negatively correlated with triglyceride (TG),free fatty acid(FFA).Acetylcholine-induced relaxation was markedly decreased in all experimental groups compared with that in NC group and the maximal response was decreased 37.4% in HSF group,32.7% in HUF group,27.7% in HS group.Acetylcholine-induced relaxation was enhanced by incubation with L-Arg and decreased incubated with L-NNA,MB in all experimental groups.Vasodilation response was negatively correlated with TG,INS and well positively correlated with NO,GIR.There was significantly negative correlation between FFA andNO.Conclusions: The rats fed high sucrose,high saturated fatty acid and high unsaturated fatty acid diets developed insulin resistance with reduced endothelium-dependent vasodilation function.

Objective To observe the effect of fenofibrate intervention on high-fructose-feeding-induced liver steatosis in rats and explore the possible mechanism. Methods Male Wistar rats were randomly divided into control group ,high fructose group and fenofibrate group[fenofibrate intervention started after 8 weeks of high fructose feeding ,30 mg/(kg · d)]. Rats were sacrificed after 12-week of high fructose feeding. Serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),total cholesterol(TC),free triglyceride(TG)and liver TG content were determined;protein levels of fatty acid synthase(FAS),endoplasmic reticulum stress mark-er Bip and autophagy markers such as Atg7,Beclin1,LC3 and the related pathway mTOR in liver tissues were de-tected. Results Compared with those in control group and fenofibrate group,serum AST,serum total cholesterol, blood free TG and hepatic TG were significantly increased in high-fructose group(P < 0.01). The protein expres-sion of Fas,Bip and mTOR were significantly increased in high-fructose group compared with those in control group and fenofibrate group;the protein expression of Atg7,beclin1 and LC3 were significantly decreased in high-fructose group compared with those in control group and fenofibrate group. Conclusions Long-term high-fructose-feeding induces fatty liver and liver cell injury ,and may affect ERS and autophagy. High-fructose-feeding-in-duced fatty liver may be improved by fenofibrate and its underlying mechanism might be associated with Fas,ERS and autophagy in liver.

Objective To explore the effect of dietary fat acids on incretin and islet function in healthy adults .Methods Before each test, healthy subjects received a 1-week pre-experiment eucaloric diet .Fifteen subjects consumed two meals containing different fat acids , including high saturated fat acid ( HSF) and high monounsaturated fat acid ( HMF) .On two separate occasions,they underwent a minimum of 1-week washout between meals .At 0,30,60,120,180 and 240 min following meal intake, the plasma concentrations of gastric inhibitory polypeptide (GIP), glucagon-like peptide-1(GLP-1) and serum concentrations of glucose, insulin, triglycerides ( TG) and free fatty acid ( FFA) were measured.Results Postprandial glucose did not increase significantly following HSF and HMF meals (P>0.05).Compared with HMF meal, significant increase in AUCins240min,AUCTG240min and AUCFFA240minwas observed following HSF meal (P<0.05).Compared with HMF meal,a significant decrease in AUCGIP30min, AUCGIP240min, AUCGLP-1 30min and AUCGLP-1 240min was found following HSF meal (P<0.05).No significant difference was observed inΔI30/ΔG30 following HSF and HMF meals (P>0.05). AUCI/AUCG was significantly lower following HMF meal as compared with HSF meal (P<0.05).Conclusion This study demonstrates that the function of GIP ,GLP-1 andβcell is affected by the dietary fat acids in healthy adults .The HMF meal may stimulate GIP and GLP-1 secretion to a greater extent than HSF meal .

Objective To study the relationship between oxidative stress and endothelial progenitor cells(EPCs)count in the first-degree relatives of diabetes mellitus(FDRs).Methods Three groups were evaluated with 40 type 2 diabetes mellitus(T2DM)patients,38 FDRs and 30 healthy individuals as the control(NC).Fasting plasma glucose(FPG),glycosylated hemoglobin(HbA1c),TG,TC and fasting plasma insulin concentrations were measured and homeostasis model assessment-insulin resistance(HOMAIR)was calculated.Quantity of EPCs and flow-mediated dilation(FMD)were evaluated.Malonaldehyde(MDA),glutathion peroxidase(GSH-Px),erythrocuprein(SOD)and total anti-oxidative capacity(TAO-C)were measured.Results In T2DM group FPG[(7.86 ±0.77)mmol/L]and HbA1c[(7.24 ±0.20)％]were significantly higher than those in NC[FPG(4.90 ± 0.35)mmol/L,HbA1 c(5.34 ± 0.37)％]and FDRsgroup[FPG(5.13±0.95)mmol/L,HbA1c(5.36 ±0.36)％](all P values ＜0.05).TC in T2DM group[(5.88 ±0.76)mmol/L]was higher than in NC[(4.66±0.90)mmol/L]and FDRs [(4.95 ± 0.76)mmol/L].HOMA-IR was 0.48 ± 0.25 in NC,0.81 ± 0.46 in FDRs and 1.47 ± 0.24 in T2DM group,P ＜ 0.01.In T2DM group,the plasma levels of SOD[(69.30 ± 2.21)U/ml],TAO-C [(7.30 ± 0.29)U/ml]and GSH-Px[(856.5 ± 9.01)U/ml]were significantly lower than those in NC [SOD(75.33 ±3.63)U/ml,TAO-C(8.17 ±0.58)U/ml and GSH-Px(938.1 ± 19.35)U/ml]and FDRs group[SOD(74.91 ±4.53)U/ml,TAO-C(8.24 ±0.46)U/ml and GSH-Px(936.9 ± 15.78)U/ml](all P values ＜ 0.01).Serum level of MDA was(2.87 ± 0.63)μmol/L in NC,(3.28 ± 0.71)μmol/L in FDRs and(3.69 ± 0.39)μmol/L in T2DM group(P ＜ 0.01).The quantity of EPCs and FMD％ were 96.75 ±8.11 and 8.36 ± 2.21 in NC,83.34 ± 12.43 and 6.78 ± 0.98 in FDRs and 58.45 ± 7.58 and 2.86 ± 0.35 in T2DM group with statistical differences between different groups(all P values ＜ 0.05).Pearson correlation analysis showed that lnHOMA-IR was positively correlated with MDA(r =0.486,P ＜0.05)and negatively correlated with SOD,TAO-C,GSH-Px(r =-0.426,-0.601,-0.524,all P values ＜ 0.05)in FDRs group.Conclusions Insulin resistance,oxidative stress,decreased quantity of EPCs and impairment of endovascular function have already occurred in the FDRs of T2DM with normal glucose tolerance and they are correlated with each other.