ABSTRACT
β-cells may turn into other pancreatic islet cells through dedifferentiation.The dedifferentiation cells lose the ability of insulin secretion.Islet β-cell dedifferentiation is the important cause of β-cell dysfunction, which then leads to the occurrence of type 2 diabetes.Rescent research shows that many transcription factors play an important role in β-cell dedifferentiation,including forkhead box protein O1,NKX2.2,NKX6.1,MAFA and MAFB.In this paper, the influence factors of β-cell dedifferentiation and its mechanism were reviewed briefly.The discovery of β-cell dedifferen-tiation provides new thoughts and targets for prevention and treatment of type 2 diabetes.
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Objective To evaluate the relationship between thioredoxin-interacting protein(TXNIP) and pancreaticβ-cell function in impaired glucose tolerance patients with and without hypertriglyceridemia. Methods A total of 267 subjects were enrolled in this study and divided into three groups:impaired glucose tolerance(IGT)group(n= 90),impaired glucose tolerance and hypertriglyceridemia(IGT +HTG)group(n=87)and normal glucose tolerance(NGT)group(n=90). The levels of plasma TXNIP were measured. Intravenous glucose tolerance test was performed to evaluate the first-phase insulin response(FPIR). HOMA forβ-cell function(HOMA-β)was calculated to evaluate basal pancreatic β-cell function. Results TXNIP was significantly higher in IGT group than in NGT group(P＜ 0.05). TXNIP was much higher in IGT+ HTG group than in IGT group (P＜0.05). HOMA-βand FPIR were decreased gradually from NGT,IGT to IGT + HTG(P＜0.05). Correlation analysis showed that HOMA-β and FPIR were negatively correlated with TXNIP(P＜ 0.05). Conclusion The level of TXNIP is increased in IGT,especially in IGT with hypertriglyceridemia. Basal and first-phase isletβ-cell function are all associated with TXNIP.
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BACKGROUND AND OBJECTIVES: In advanced β-cell dysfunction, proinsulin is increasingly replacing insulin as major component of the secretion product. It has been speculated that proinsulin has at least the same adipogenic potency than insulin, leading to an increased tendency of lipid tissue formation in patients with late stage β-cell dysfunction. METHODS AND RESULTS: Mesenchymal stem cells obtained from liposuction material were grown in differentiation media containing insulin (0.01 μmol), proinsulin (0.01 μmol) or insulin+proinsulin (each 0.005 μmol). Cell culture supernatants were taken from these experiments and an untreated control at weeks 1, 2, and 3, and were stored at −80°C until analysis. Cell differentiation was microscopically supervised and adiponectin concentrations were measured as marker for differentiation into mature lipid cells. This experiment was repeated three times. No growth of lipid cells and no change in adiponectin values was observed in the negative control group (after 7/14/12 days: 3.2±0.5/3.3±0.1/4.4±0.5 ng/ml/12 h). A continuous differentiation into mature adipocytes (also confirmed by Red-Oil-staining) and a corresponding increase in adiponectin values was observed in the experiments with insulin (3.6±1.9/5.1±1.4/13.3±1.5 ng/ml/12 h; p < 0.05 week 1 vs. week 3) and proinsulin (3.3±1.2/3.5±0.3/12.2±1.2 ng/ml/12 h; p < 0.05). Comparable effects were seen with the insulin/proinsulin combination. CONCLUSIONS: Proinsulin has the same adipogenic potential than insulin in vitro. Proinsulin has only 10~20% of the glucose-lowering effect of insulin. It can be speculated that the adipogenic potential of proinsulin may be a large contributor to the increased body weight problems in patients with type 2 diabetes and advanced β-cell dysfunction.
Subject(s)
Humans , Adipocytes , Adiponectin , Body Weight , Cell Culture Techniques , Cell Differentiation , In Vitro Techniques , Insulin , Lipectomy , Mesenchymal Stem Cells , ProinsulinABSTRACT
[Summary] The general status of glycemic control and insulin initiation are not optimistic in Chinese patients with type 2 diabetes.Chinese patients experience pancreatic β-cell dysfunction and reduction of early phase insulin spike earlier and more severely compared to Caucasians.These can cause more significant postprandial hyperglycaemia which is further deteriorated by traditional carbohydrate-rich Chinese diet.Therefore,premixed insulin may be a more appropriate option of insulin initiation therapy for Chinese patients with type 2 diabetes mellitus.
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To study the level of macrophage migration inhibitory factor (MIF) in serum and the expression of MIF mRNA in abdominal subcutaneous adipose tissue,and to investigate its impact on insulin resistance and islet β-cell dysfunction in gestational diabetes mellitus (GDM).120 pregnancy women from the Affiliated Hospital of Qingdao University Medical College and Taian Central Hospital were enrolled,including 60 GDM women and 60 women with normal glucose tolerance (NGT).The serum MIF in GDM group was higher than that of NGT group [(3.58±1.02 vs 1.23±0.62) ng/ml,P<0.01].Multiple stepwise regression analysis showed that body mass index was an independent affective factor of the serum levels of MIF (r2 =0.516).The serum levels of MIF and the expressions of MIF mRNA in abdominal subcutaneous adipose tissue were significantly higher in GDM group than NGT group.MIF may contribute to insulin resistance and β-cell dysfunction in GDM.Body mass index seems to be an independent factor in affecting the serum levels of MIF.