Dynamic pathology of islet endocrine cells in type 2 diabetes: β‐Cell growth, death, regeneration and their clinical implications

Abstract

Diabetes is defined as a disease of hyperglycemic metabolic disorder caused by impaired insulin action or low insulin secretion, resulting in the occurrence of vascular complications. Based on this definition, diabetes therapy has long been oriented to correct hyperglycemia against the specific complications of diabetes. This definition has posed some difficulties, however, in understanding of the pathophysiology of this complicated disease and as such in the establishment of an effective treatment. With continuing efforts to explore the structural basis for diabetes onset and methodological development of immunohistochemistry, progressive decline of β‐cells is now established as a salient feature of type 2 diabetes. Accordingly, diabetes therapy has now turned out to protect β‐cells concurrently with the correction of hyperglycemia. Together with this effort, exploration of the means to regenerate β‐cells or to supply new β‐cells by, for example, induced pluripotential stem cells, are vigorously made with the search for the mechanism of β‐cell decline in diabetes. In the present review, we describe the advances in the islet pathology in type 2 diabetes with special reference to the dynamic alterations of islet endocrine cells in the milieu of maturation, obesity, aging and ethnic differences. The effect of amyloid deposition is also discussed. We hope it will help with understanding the pathophysiology of diabetes, and suggest the future direction of diabetes treatment.

Kidney Cadmium Toxicity, Diabetes and High Blood Pressure: The Perfect Storm

“…Loss of pancreatic β-cells due to Cd-induced apoptosis may thus be another mechanism for effects of Cd exposure on pre-diabetic risk. Yagihashi et al (2016) reported a reduction in pancreatic β-cell volume density in both a diabetic, obese American group and diabetic, lean Asian (Japanese and Korean) groups, but compensatory hyperplasia of pancreatic β-cells has been evident only in the diabetic, obese American group. These observations may explain lower mortality among diabetic obese people, compared with diabetic lean persons (Engelmann et al 2016).…”

Clinical relevance of epigenetics in the onset and management of type 2 diabetes mellitus

“…Several studies report that the mass and volume of b-cells are reduced by about 30 to 60% in type 2 diabetic patients, thus creating the generalized consensus on the central role of the b-cell functional decline in the onset of T2DM. 15,16 Pathological modifications of the b-cell epigenome can cause b-cell insufficiency by impairing the maintenance of the differentiated, functional state of these cells. 17 Indeed, there are master genes responsible for the differentiation of pancreatic a-and b-cells, and epigenetic mechanisms can alter the physiologic and balanced differentiation of the common precursor cells, both during developmental stages and adult life.…”

Comparison of pancreatic volume and fat amount linked with glucose homeostasis between healthy Caucasians and Koreans

“…Compared with non-diabetic autopsy cases, β-cell volume density in Korean people with T2D was found to be 40% lower, 33 similar to that in Japanese people with T2D. 34 Although we measured pancreatic volume and not β-cell mass in this study, there is solid evidence supporting a positive association between pancreatic volume and glucose homeostasis. 16,35,36 Occupancy of β cells in the pancreatic parenchyma is known to reach the adult level at the age of 5-10 years.…”

“…There is much evidence to show that pancreatic β‐cell volume is crucial in glucose homeostasis. Compared with non‐diabetic autopsy cases, β‐cell volume density in Korean people with T2D was found to be 40% lower, similar to that in Japanese people with T2D . Although we measured pancreatic volume and not β‐cell mass in this study, there is solid evidence supporting a positive association between pancreatic volume and glucose homeostasis .…”

“…Inclusion criteria for white participants were: non-Hispanic white ethnicity; age [25][26][27][28][29][30][31][32][33][34][35] We recruited white participants first, followed by Korean participants to match age and BMI. We screened 56 white people.…”