scholarly journals Long-term hyperglucagonaemia induces early metabolic and renal phenotypes of Type 2 diabetes in mice

2008 ◽  
Vol 114 (9) ◽  
pp. 591-601 ◽  
Author(s):  
Xiao C. Li ◽  
Tang-dong Liao ◽  
Jia L. Zhuo

Clinical studies have shown that patients with early Type 2 diabetes often have elevated serum glucagon rather than insulin deficiency. Imbalance of insulin and glucagon in favouring the latter may contribute to impaired glucose tolerance, persistent hyperglycaemia, microalbuminuria and glomerular injury. In the present study, we tested the hypothesis that long-term glucagon infusion induces early metabolic and renal phenotypes of Type 2 diabetes in mice by activating glucagon receptors. Five groups of adult male C57BL/6J mice were treated with vehicle, glucagon alone (1 μg/h via an osmotic minipump, intraperitoneally), glucagon plus the glucagon receptor antagonist [Des-His1-Glu9]glucagon (5 μg/h via an osmotic minipump), [Des-His1-Glu9]glucagon alone or a high glucose load alone (2% glucose in the drinking water) for 4 weeks. Glucagon infusion increased serum glucagon by 129% (P<0.05), raised systolic BP (blood pressure) by 21 mmHg (P<0.01), elevated fasting blood glucose by 42% (P<0.01), impaired glucose tolerance (P<0.01), increased the kidney weight/body weight ratio (P<0.05) and 24 h urinary albumin excretion by 108% (P<0.01) and induced glomerular mesangial expansion and extracellular matrix deposition. These responses were associated with marked increases in phosphorylated ERK1/2 (extracellular-signal-regulated kinase 1/2) and Akt signalling proteins in the liver and kidney (P<0.01). Serum insulin did not increase proportionally. Concurrent administration of [Des-His1-Glu9]glucagon with glucagon significantly attenuated glucagon-increased BP, fasting blood glucose, kidney weight/body weight ratio and 24 h urinary albumin excretion. [Des-His1-Glu9]glucagon also improved glucagon-inpaired glucose tolerance, increased serum insulin by 56% (P<0.05) and attenuated glomerular injury. However, [Des-His1-Glu9]glucagon or high glucose administration alone did not elevate fasting blood glucose levels, impair glucose tolerance or induce renal injury. These results demonstrate for the first time that long-term hyperglucagonaemia in mice induces early metabolic and renal phenotypes of Type 2 diabetes by activating glucagon receptors. This supports the idea that glucagon receptor blockade may be beneficial in treating insulin resistance and Type 2 diabetic renal complications.

1970 ◽  
Vol 36 (2) ◽  
pp. 47-51 ◽  
Author(s):  
MA Rahim ◽  
AK Azad Khan ◽  
Quamrun Nahar ◽  
SMK Ali ◽  
Akhtar Hussain

The prevalence of type 2 diabetes is rapidly rising all over the world at an alarming rate. Over the past 30 years, the increase in prevalence is rising exponentially in South Asian region, data suggest a three fold increase (from 2.0 to 7.0%) in the urbanizing population of Bangladesh within 5 years. However, the prevalence of various degrees of glucose intolerance i.e. type 2 diabetes, impaired glucose tolerance and impaired fasting glucose considered vital for prevention are still unknown in this population. The objective of the study was to estimate the prevalence of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) and type 2 diabetes (T2DM) with their demographic and anthropometric characteristics in a reasonable large sample compare to other studies conducted in Bangladesh. A random sample of 5000 rural population aged ≥ 20 years was included in this cross sectional study. Fasting blood glucose (FBG) level was measured from 3981 individuals and 2-hr blood glucose (BG) was done on 3954 subjects, excluding known diabetic cases (n= 27). Height, weight, waist and hip circumference including blood pressure and demographic information was also collected. The prevalence of impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and newly detected type 2 diabetes (T2DM) were 1.3%, 2.0% and 7.0% respectively. IFG, IGT, IFG+IGT were more prevalent in females than males. Age, body mass index (BMI), waist circumference (WC) and waist to hip ratio (WHR) were higher in glucose–intolerant subjects than in normal glucose tolerant (NGT) group. FBG and 2-hr BG values were correlated in NGT and DM subjects. Our data suggest that estimation of FBG value identifies more people with diabetes compared to 2-hr BG estimation. These findings need to be further examined in other settings with urban and rural populations for the justification of FBG for screening of diabetes in Bangladeshi population for development of intervention strategy for the prevention and management of abnormal glucose tolerance. The significance of IFG as a precursor of diabetes and CVD will become evident only from longitudinal studies in different ethnic groups. DOI: 10.3329/bmrcb.v36i2.6986Bangladesh Med Res Counc Bull 2010; 36: 47-51


2012 ◽  
Vol 2012 ◽  
pp. 1-4 ◽  
Author(s):  
Xiaodan Li ◽  
Zhuqin Yu ◽  
Shaohua Long ◽  
Yunliang Guo ◽  
Delin Duan

The aim is to investigate the hypoglycemic effect of Laminaria japonica polysaccharides (LJPS) on type 2 diabetes mellitus (T2DM) mice model. 60 healthy male mice have been used in the experiment. T2DM animal mode was prepared by high fatty forage feeding and intraperitoneal injection with alloxan. Diabetic mice were orally supplied with LJPS. Then their blood was collected for various biomedical measurements of fasting blood glucose (FBG), serum insulin, and amylin. Treatment with LJPS significantly reduced fasting blood glucose (P<0.05) and increased the levels of insulin and amylin in serum (P<0.05). Overall, the study presented that LJPS can reverse several components of T2DM. Therefore, LJPS may become a new oral candidate medicine for the treatment of diabetes.


2021 ◽  
Vol 8 ◽  
Author(s):  
Mohammad Ishraq Zafar ◽  
Michael Frese ◽  
Kerry E. Mills

Despite the publication of several of meta-analyses in recent years, the effects of fructose on human health remains a topic of debate. We previously undertook two meta-analyses on post-prandial and chronic responses to isoenergetic replacement of fructose for sucrose or glucose in food or beverages (Evans et al. 2017, AJCN 106:506–518 &amp; 519–529). Here we report on the results of an updated search with a complete re-extraction of previously identified studies and a new and more detailed subgroup-analysis and meta-regression. We identified two studies that were published after our previous analyses, which slightly altered effect sizes and conclusions. Overall, the isoenergetic substitution of fructose for glucose resulted in a statistically significant but clinically irrelevant reduction in fasting blood glucose, insulin, and triglyceride concentrations. A subgroup analysis by diabetes status revealed much larger reductions in fasting blood glucose in people with impaired glucose tolerance and type 2 diabetes. However, each of these subgroups contained only a single study. In people with a healthy body mass index, fructose consumption was associated with statistically significant, but clinically irrelevant reductions in fasting blood glucose and fasting blood insulin. Meta-regression of the outcomes by a number of pre-identified and post-hoc covariates revealed some sources of heterogeneity, such as year of publication, age of the participants at baseline, and participants' sex. However, the small number of studies and the large number of potential covariates precluded detailed investigations of effect sizes in different subpopulations. For example, well-controlled, high quality studies in people with impaired glucose tolerance and type 2 diabetes are still lacking. Taken together, the available data suggest that chronic consumption of fructose is neither more beneficial, nor more harmful than equivalent doses of sucrose or glucose for glycemic and other metabolic outcomes.


Epigenomics ◽  
2021 ◽  
Author(s):  
Marwa Matboli ◽  
Doaa Ibrahim ◽  
Amany H Hasanin ◽  
Mohamed Kamel Hassan ◽  
Eman K Habib ◽  
...  

Aim: To assess isorhamnetin efficacy for diabetic kidney disease in a Type 2 diabetes mellitus rat model, through investigating its effect at the epigenetic, mRNA and protein levels. Materials & methods: Type 2 diabetes mellitus was induced in rats by streptozotocin and high-fat diet. Rats were treated with isorhamnetin (50 mg/kg/d) for 4 or 8 weeks. Fasting blood glucose, renal and lipid profiles were evaluated. Renal tissues were examined by light and electron microscopy. Autophagy genes ( FYCO1, ULK, TECPR1 and  WIPI2) and miR-15b, miR-34a and miR-633 were assessed by qRT-PCR, and LC3A/B by immunoblotting. Results: Isorhamnetin improved fasting blood glucose, renal and lipid profiles with increased autophagosomes in renal tissues. It suppressed miRNA regulation of autophagy genes Conclusion: We propose a molecular mechanism for the isorhamnetin renoprotective effect by modulation of autophagy epigenetic regulators.


2020 ◽  
Vol 45 (4) ◽  
pp. 397-404
Author(s):  
Tugba Gurpinar Çavuşoğlu ◽  
Ertan Darıverenli ◽  
Kamil Vural ◽  
Nuran Ekerbicer ◽  
Cevval Ulman ◽  
...  

AbstractObjectivesType 2 diabetes is a common metabolic disease and anxiety disorders are very common among diabetics. Buspirone is used in the treatment of anxiety, also having blood glucose-lowering effects. The aim of the study was to investigate the effects of buspirone on the glucose and lipid metabolism as well as vascular function in type 2 diabetic rats.MethodsA type 2-diabetic model was induced through a high-fat diet for eight weeks followed by the administration of low-dose streptozotocin (35 mg/kg, intraperitoneal) in rats. Buspirone was given at two different doses (1.5 mg/kg/d and 5 mg/kg/d) and combined with metformin (300 mg/kg/d). The fasting glucose and insulin levels, lipid profile were analyzed, and vascular response measured from the thoracic aorta was also evaluated.ResultsBoth doses of buspirone caused a significant improvement in fasting blood glucose levels. In particular, the buspirone treatment, combined with metformin, improved endothelial dysfunction and was found to be correlated with decreased nitrate/nitrite levels.ConclusionsBuspirone may be effective in the treatment of type 2 diabetes, either alone or in combination with other treatments, particularly in terms of endothelial dysfunction, inflammation and impaired blood glucose, and insulin levels.


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