scholarly journals Reduced beta cell number rather than size is a major contributor to beta cell loss in type 2 diabetes

Diabetologia ◽  
2021 ◽  
Author(s):  
Hironobu Sasaki ◽  
Yoshifumi Saisho ◽  
Jun Inaishi ◽  
Yuusuke Watanabe ◽  
Tami Tsuchiya ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Beta Cell ◽  
Cell Size ◽  
Cell Mass ◽  
Cell Number ◽  
Relative Reduction ◽  
Major Contributor ◽  
Islet Morphology ◽  
The Impact

Abstract Aims/hypothesis Type 2 diabetes is characterised by reduced beta cell mass (BCM). However, it remains uncertain whether the reduction in BCM in type 2 diabetes is due to a decrease in size or number of beta cells. Our aim was to examine the impact of beta cell size and number on islet morphology in humans with and without type 2 diabetes. Methods Pancreas samples were obtained from 64 Japanese adults with (n = 26) and without (n = 38) type 2 diabetes who underwent pancreatectomy. Using pancreatic tissues stained for insulin, we estimated beta cell size based on beta cell diameter. Beta cell number was estimated from the product of fractional beta cell area and pancreas volume divided by beta cell size. The associations of beta cell size and number with islet morphology and metabolic status were examined. Results Both beta cell size (548.7 ± 58.5 vs 606.7 ± 65.0 μm3, p < 0.01) and number (5.10 × 108 ± 2.35 × 108 vs 8.16 × 108 ± 4.27 × 108, p < 0.01) were decreased in participants with type 2 diabetes compared with those without diabetes, with the relative reduction in beta cell number (37%) being greater than for beta cell size (10%). Beta cell number but not size was positively correlated with BCM in participants with and without type 2 diabetes (r = 0.97 and r = 0.98, both p < 0.01) and negatively correlated with HbA1c (r = −0.45, p < 0.01). Conclusions/interpretation Both beta cell size and number were reduced in participants with type 2 diabetes, with the relative reduction in beta cell number being greater. Decrease in beta cell number appears to be a major contributor to reduced BCM in type 2 diabetes. Graphical abstract

scholarly journals A Novel Mouse Model for Type 2 Diabetes and Non-alcoholic Fatty Liver Disease: Spontaneous Amelioration of Diabetes by Augmented Beta Cell Mass

2009 ◽  
Vol 56 (2) ◽  
pp. 227-234 ◽  
Author(s):  
Aya OZE-FUKAI ◽  
Tomomi FUJISAWA ◽  
Ken SUGIMOTO ◽  
Koji NOJIMA ◽  
Nobuyasu SHINDO ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Liver Disease ◽  
Mouse Model ◽  
Beta Cell ◽  
Fatty Liver Disease ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

scholarly journals Imprinted Genes Impact Upon Beta Cell Function in the Current (and Potentially Next) Generation

2021 ◽  
Vol 12 ◽  
Author(s):  
Chelsie Villanueva-Hayes ◽  
Steven J. Millership
Keyword(s):  
Type 2 Diabetes ◽  
Beta Cell ◽  
Beta Cells ◽  
Cell Function ◽  
Monoallelic Expression ◽  
Imprinted Genes ◽  
Nutritional Regulation ◽  
Next Generation ◽  
The Impact

Beta cell failure lies at the centre of the aetiology and pathogenesis of type 2 diabetes and the epigenetic control of the expression of critical beta cell genes appears to play a major role in this decline. One such group of epigenetically-controlled genes, termed ‘imprinted’ genes, are characterised by transgenerational monoallelic expression due to differential allelic DNA methylation and play key functional roles within beta cells. Here, we review the evidence for this functional importance of imprinted genes in beta cells as well as their nutritional regulation by the diet and their altered methylation and/or expression in rodent models of diabetes and in type 2 diabetic islets. We also discuss imprinted genes in the context of the next generation, where dietary overnutrition in the parents can lead to their deregulation in the offspring, alongside beta cell dysfunction and defective glucose handling. Both the modulation of imprinted gene expression and the likelihood of developing type 2 diabetes in adulthood are susceptible to the impact of nutritional status in early life. Imprinted loci, therefore, represent an excellent opportunity with which to assess epigenomic changes in beta cells due to the diet in both the current and next generation.

scholarly journals Verapamil can be used as a Type 2 Diabetes Mellitus Saviour and Stopping the need for Insulin in Uncontrolled Type 2 Diabetes Mellitus

2021 ◽  
pp. 1-8
Author(s):  
Mahmoud Younis ◽  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Beta Cell ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Interacting Protein ◽  
Significant Difference ◽  
And Function

Introduction: Diabetes mellitus is not just a disease as it is already known, the matter is more complicated, and it is considered as an assembly of metabolic defects with end result of hyperglycemia.verapamil can decrease the expression of thioredoxin-interacting protein (TXNIP), which is recognized as an important factor in pancreatic beta cells.verapamil could enhance beta cell mass and function. Materials and Methods: 160 type 2 diabetes patients in 2 parallel groups. Results: show statistically significant difference in favour of verapamil in increasing c-peptide levels and decreasing hba1c levels. Conclusion: Verapamil could be used as a type 2 diabetes saviour by increasing beta cell mass and function.

scholarly journals Beta-Cell Mass in Obesity and Type 2 Diabetes, and Its Relation to Pancreas Fat: A Mini-Review

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3846
Author(s):  
Jun Inaishi ◽  
Yoshifumi Saisho
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Beta Cell ◽  
Current Knowledge ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Beta Cell Dysfunction ◽  
Cell Dysfunction ◽  
Pancreatic Fat

Type 2 diabetes (T2DM) is characterized by insulin resistance and beta-cell dysfunction. Although insulin resistance is assumed to be a main pathophysiological feature of the development of T2DM, recent studies have revealed that a deficit of functional beta-cell mass is an essential factor for the pathophysiology of T2DM. Pancreatic fat contents increase with obesity and are suggested to cause beta-cell dysfunction. Since the beta-cell dysfunction induced by obesity or progressive decline with disease duration results in a worsening glycemic control, and treatment failure, preserving beta-cell mass is an important treatment strategy for T2DM. In this mini-review, we summarize the current knowledge on beta-cell mass, beta-cell function, and pancreas fat in obesity and T2DM, and we discuss treatment strategies for T2DM in relation to beta-cell preservation.

scholarly journals The Phosphatase PHLPP2 Plays a Key Role in the Regulation of Pancreatic Beta-Cell Survival

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Marta Letizia Hribal ◽  
Elettra Mancuso ◽  
Gaetano Paride Arcidiacono ◽  
Annalisa Greco ◽  
Donatella Musca ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Beta Cell ◽  
Cell Survival ◽  
High Glucose ◽  
Chronic Exposure ◽  
Pancreatic Beta Cell ◽  
Cell Mass ◽  
Pleckstrin Homology Domain ◽  
Causative Role

Currently available antidiabetic treatments fail to halt, and may even exacerbate, pancreatic β-cell exhaustion, a key feature of type 2 diabetes pathogenesis; thus, strategies to prevent, or reverse, β-cell failure should be actively sought. The serine threonine kinase Akt has a key role in the regulation of β-cell homeostasis; among Akt modulators, a central role is played by pleckstrin homology domain leucine-rich repeat protein phosphatase (PHLPP) family. Here, taking advantage of an in vitro model of chronic exposure to high glucose, we demonstrated that PHLPPs, particularly the second family member called PHLPP2, are implicated in the ability of pancreatic β cells to deal with glucose toxicity. We observed that INS-1 rat pancreatic β cell line maintained for 12–15 passages at high (30 mM) glucose concentrations (INS-1 HG) showed increased expression of PHLPP2 and PHLPP1 both at mRNA and protein level as compared to INS-1 maintained for the same number of passages in the presence of normal glucose levels (INS-1 NG). These changes were paralleled by decreased phosphorylation of Akt and by increased expression of apoptotic and autophagic markers. To investigate if PHLPPs had a casual role in the alteration of INS-1 homeostasis observed upon chronic exposure to high glucose concentrations, we took advantage of shRNA technology to specifically knock-down PHLPPs. We obtained proof-of-concept evidence that modulating PHLPPs expression may help to restore a healthy β cell mass, as the reduced expression of PHLPP2/1 was accompanied by a recovered balance between pro- and antiapoptotic factor levels. In conclusion, our data provide initial support for future studies aimed to identify pharmacological PHLPPs modulator to treat beta-cell survival impairment. They also contribute to shed some light on β-cell dysfunction, a complex and unsatisfactorily characterized phenomenon that has a central causative role in the pathogenesis of type 2 diabetes.

scholarly journals ZRANB3 is an African-specific type 2 diabetes locus associated with beta-cell mass and insulin response

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Adebowale A. Adeyemo ◽  
◽  
Norann A. Zaghloul ◽  
Guanjie Chen ◽  
Ayo P. Doumatey ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Beta Cell ◽  
Cell Mass ◽  
Insulin Response ◽  
Beta Cell Mass
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