scholarly journals Beta-Cell Dysfunction Induced by Tacrolimus: A Way to Explain Type 2 Diabetes?

2021 ◽  
Vol 22 (19) ◽  
pp. 10311
Author(s):  
Ana Elena Rodriguez-Rodriguez ◽  
Esteban Porrini ◽  
Armando Torres
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Renal Transplant Recipients ◽  
Β Cells ◽  
Cell Dysfunction ◽  
Nuclear Factors ◽  
Onset Of Diabetes ◽  
Serious Disease

The combination of insulin resistance and β-cells dysfunction leads to the onset of type-2 diabetes mellitus (T2DM). This process can last for decades, as β-cells are able to compensate the demand for insulin and maintain normoglycemia. Understanding the adaptive capacity of β-cells during this process and the causes of its failure is essential to the limit onset of diabetes. Post-transplant diabetes mellitus (PTDM) is a common and serious disease that affects 30% of renal transplant recipients. With the exception of immunosuppressive therapy, the risk factors for T2D are the same as for PTDM: obesity, dyslipidaemia, insulin resistance and metabolic syndrome. Tacrolimus (TAC) is the immunosuppressant of choice after renal transplantation but it has the highest rates of PTDM. Our group has shown that insulin resistance and glucolipotoxicity, without favouring the appearance of apoptosis, modify key nuclear factors for the maintenance of identity and functionality of β-cells. In this context, TAC accelerates or enhances these changes. Our hypothesis is that the pathways that are affected in the progression from pre-diabetes to diabetes in the general population are the same pathways that are affected by TAC. So, TAC can be considered a tool to study the pathogenesis of T2DM. Here, we review the common pathways of β-cells dysfunction on T2DM and TAC-induced diabetes.

scholarly journals Risk Factors for Type 2 Diabetes Mellitus Preceded by β-Cell Dysfunction, Insulin Resistance, or Both in Older Adults

2013 ◽  
Vol 177 (12) ◽  
pp. 1418-1429 ◽  
Author(s):  
Fumiaki Imamura ◽  
Kenneth J. Mukamal ◽  
James B. Meigs ◽  
José A. Luchsinger ◽  
Joachim H. Ix ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factors ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Older Adults ◽  
Type 2 Diabetes Mellitus ◽  
Β Cell ◽  
Cell Dysfunction

scholarly journals Insulin: The Friend and the Foe in the Development of Type 2 Diabetes Mellitus

2020 ◽  
Vol 21 (5) ◽  
pp. 1770
Author(s):  
Nadia Rachdaoui
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Insulin Secretion ◽  
Cell Mass ◽  
Β Cells ◽  
Β Cell ◽  
Peripheral Insulin Resistance

Insulin, a hormone produced by pancreatic β-cells, has a primary function of maintaining glucose homeostasis. Deficiencies in β-cell insulin secretion result in the development of type 1 and type 2 diabetes, metabolic disorders characterized by high levels of blood glucose. Type 2 diabetes mellitus (T2DM) is characterized by the presence of peripheral insulin resistance in tissues such as skeletal muscle, adipose tissue and liver and develops when β-cells fail to compensate for the peripheral insulin resistance. Insulin resistance triggers a rise in insulin demand and leads to β-cell compensation by increasing both β-cell mass and insulin secretion and leads to the development of hyperinsulinemia. In a vicious cycle, hyperinsulinemia exacerbates the metabolic dysregulations that lead to β-cell failure and the development of T2DM. Insulin and IGF-1 signaling pathways play critical roles in maintaining the differentiated phenotype of β-cells. The autocrine actions of secreted insulin on β-cells is still controversial; work by us and others has shown positive and negative actions by insulin on β-cells. We discuss findings that support the concept of an autocrine action of secreted insulin on β-cells. The hypothesis of whether, during the development of T2DM, secreted insulin initially acts as a friend and contributes to β-cell compensation and then, at a later stage, becomes a foe and contributes to β-cell decompensation will be discussed.

The involvement of microRNAs in Type 2 diabetes

2010 ◽  
Vol 38 (6) ◽  
pp. 1565-1570 ◽  
Author(s):  
David Ferland-McCollough ◽  
Susan E. Ozanne ◽  
Kenneth Siddle ◽  
Anne E. Willis ◽  
Martin Bushell
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Molecular Mechanisms ◽  
Genetic Factors ◽  
Β Cells ◽  
Major Health ◽  
Cell Dysfunction ◽  
Metabolic Genes ◽  
Major Health Issue

T2D (Type 2 diabetes mellitus) is a major health issue that has reached epidemic status worldwide. T2D is a progressive metabolic disorder characterized by reduced insulin sensitivity, insulin resistance and pancreatic β-cell dysfunction. Improper treatment of TD2 can lead to severe complications such as heart disease, stroke, kidney failure, blindness and nerve damage. The aetiology and molecular mechanisms of T2D are not fully understood, but compelling evidence points to a link between T2D, obesity, dyslipidaemia and insulin resistance. Although T2D seems to be strongly linked to environmental factors such as nutrition and lifestyle, studies have shown that genetic factors, such as polymorphisms associated with metabolic genes, imprinting, fetal programming and miRNA (microRNA) expression, could also contribute to the development of this disease. miRNAs are small 22–25-nt-long untranslated RNAs that negatively regulate the translation of mRNAs. miRNAs are involved in a large number of biological functions such as development, metabolism, immunity and diseases such as cancer, cardiovascular diseases and diabetes. The present review examines the various miRNAs that have been identified as being potentially involved in T2D, focusing on the insulin-sensitive organs: white adipose tissue, liver, skeletal muscle and the insulin-producing pancreatic β-cells.

Abstract 008: Risk Factors for Type 2 Diabetes Mellitus Preceded by β-cell Dysfunction, Insulin Resistance, or Both: The Cardiovascular Health Study

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Fumiaki Imamura ◽  
Kenneth J Mukamal ◽  
James B Meigs ◽  
Jose A Luchsinger ◽  
Joachim H Ix ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factors ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Older Adults ◽  
Fasting Glucose ◽  
Β Cell ◽  
Cell Dysfunction

Background: Type 2 diabetes mellitus (DM) results from insulin resistance (IR), pancreatic β-cell dysfunction, or both. We hypothesized that risk factors could differ for DM preceded predominantly by IR, β-cell dysfunction, or both. This hypothesis is particularly important for older adults, in whom β-cell dysfunction may be relatively common. Methods: During 18 years of follow-up among 3,899 older adults free of DM (mean±sd age =73.0±5.8), we identified 274 incident DM cases by DM medication use, fasting glucose (≥126 mg/dL), or 2-hour post-challenge glucose (≥200 mg/dL), for whom homeostatic model assessments for IR (HOMA-IR) and β-cell function (HOMA-B) were assessed after baseline and before DM diagnosis. Using median cutoffs of the follow-up HOMA-IR and HOMA-B, we subclassified incident DM into DM preceded by IR only (n=112), β-cell dysfunction only (n=70), or both (n=77). Using multivariate competing-risk Cox models, we tested whether DM risk factors were differentially associated with risk of each DM subclass. Results: Elevated triglyceride levels (≥150 mg/dL) and impaired fasting glucose (100-125 mg/dL) were each positively associated with DM, irrespective of the DM subclass. Other DM risk factors of older age, overweight, obesity, low HDL cholesterol, and hypertension had substantially varying relationships with risk of different DM subclasses (p<0.001 for the variations). For example, overweight (BMI=25-29.9 kg/m2) and obesity (BMI≥30 kg/m2) were each positively associated with DM preceded by IR only (hazard ratio [95% CI]= 2.21 [1.25-3.92] and 5.02 [2.81-9.00], respectively), but with a significant inverse association with DM preceded by β-cell dysfunction only (0.61 [0.37-1.00] and 0.33 [0.14-0.80], respectively) (Figure). Conclusions: Among older adults, some DM risk factors differ substantially depending on HOMA-IR or HOMA-B subclassification. These findings support our hypothesis of heterogeneity in incident DM, especially among older adults.

scholarly journals Vildagliptin: optimal control in type 2 diabetes mellitus treatment

2015 ◽  
Vol 18 (4) ◽  
pp. 125-129
Author(s):  
Alexander Sergeevich Ametov
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Clinical Evidence ◽  
Β Cells ◽  
Postprandial Triglyceride ◽  
Impaired Insulin ◽  
Diabetes Mellitus Treatment

Incretin hormones are important for normal pancreatic islet function and glucose homeostasis. Sensitivity to glucose of the α- and β-cells of the pancreas is diminished in type 2 diabetes mellitus (T2DM), leading to impaired insulin secretion, insulin resistance due to elevated glucagon levels in hyperglycaemia and impaired glucagon counterregulation in hypoglycaemia. In addition, T2DM is associated with increased lipotoxicity-induced insulin resistance. This article is a comprehensive review of the safety and efficacy of vildagliptin in patients with T2DM and evaluates the extra-pancreatic effects of incretin-based therapies. Clinical evidence has proven that vildagliptin effectively decreases HbA1c with a low risk of hypoglycaemia and is weight neutral. Vildagliptin also suppresses postprandial triglyceride (TG)-rich lipoprotein levels after ingestion of fat-rich meals and reduces fasting lipolysis, suggesting inhibition of fat absorption and reduced TG stores in non-fat tissues.

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