Failure of beta-cell adaptation in type 2 diabetes: Lessons from animal models

Metabolic surgery is the most efficacious method for the treatment of morbid obesity and was recently included among the antidiabetes treatments recommended in obese type 2 diabetes (T2D) patients. The aim of this study was to compare in a randomized controlled trial the effect of sleeve gastrectomy (SG) to that of intensive lifestyle intervention plus pharmacologic treatment on some markers of insulin resistance and beta cell function as well as some appetite controlling hormones in a group of male obese T2D subjects. The study groups comprised 20 subjects for SG and 21 control subjects. Fasting blood glucose, insulin, proinsulin, adiponectin, leptin, ghrelin, HOMA-IR, HOMA-%B, proinsulin-to-insulin ratio and proinsulin-to-adiponectin ratio were evaluated at baseline and after one year follow-up. Overall, patients in the SG group lost 78.98% of excess weight loss (%EWL) in comparison with 9.45% in the control group. This was accompanied by a significant improvement of insulin resistance markers, including increase of adiponectin and decrease of HOMA-IR, while no changes were recorded in the control group. Weight loss was also associated with a significant improvement of proinsulin-to-insulin and proinsulin-to-adiponectin ratio, both surrogate markers of beta cell dysfunction. These also improved in the control group, but were only marginally significant. Our findings suggest that improved insulin resistance and decreased beta cell dysfunction after sleeve gastrectomy might explain diabetes remission associated with metabolic surgery.

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

Diabetologia ◽

10.1007/s00125-021-05467-7 ◽

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

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A Common Functional Regulatory Variant at a Type 2 Diabetes Locus Upregulates ARAP1 Expression in the Pancreatic Beta Cell

The American Journal of Human Genetics ◽

10.1016/j.ajhg.2013.12.011 ◽

2014 ◽

Vol 94 (2) ◽

pp. 186-197 ◽

Cited By ~ 43

Author(s):

Jennifer R. Kulzer ◽

Michael L. Stitzel ◽

Mario A. Morken ◽

Jeroen R. Huyghe ◽

Christian Fuchsberger ◽

...

Keyword(s):

Type 2 Diabetes ◽

Beta Cell ◽

Pancreatic Beta Cell ◽

Regulatory Variant

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Spontaneous Type 2 Diabetic Rodent Models

Journal of Diabetes Research ◽

10.1155/2013/401723 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 22

Author(s):

Yang-wei Wang ◽

Guang-dong Sun ◽

Jing Sun ◽

Shu-jun Liu ◽

Ji Wang ◽

...

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Health Care ◽

Animal Models ◽

Rodent Models ◽

Advantages And Disadvantages ◽

Characteristic Features ◽

Type 2 Diabetic

Diabetes mellitus, especially type 2 diabetes (T2DM), is one of the most common chronic diseases and continues to increase in numbers with large proportion of health care budget being used. Many animal models have been established in order to investigate the mechanisms and pathophysiologic progress of T2DM and find effective treatments for its complications. On the basis of their strains, features, advantages, and disadvantages, various types of animal models of T2DM can be divided into spontaneously diabetic models, artificially induced diabetic models, and transgenic/knockout diabetic models. Among these models, the spontaneous rodent models are used more frequently because many of them can closely describe the characteristic features of T2DM, especially obesity and insulin resistance. In this paper, we aim to investigate the current available spontaneous rodent models for T2DM with regard to their characteristic features, advantages, and disadvantages, and especially to describe appropriate selection and usefulness of different spontaneous rodent models in testing of various new antidiabetic drugs for the treatment of type 2 diabetes.

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