Islet β cell mass in diabetes and how it relates to function, birth, and death

In type 1 diabetes (T1D) β cell mass is markedly reduced by autoimmunity. Type 2 diabetes (T2D) results from inadequate β cell mass and function that can no longer compensate for insulin resistance. The reduction of β cell mass in T2D may result from increased cell death and/or inadequate birth through replication and neogenesis. Reduction in mass allows glucose levels to rise, which places β cells in an unfamiliar hyperglycemic environment, leading to marked changes in their phenotype and a dramatic loss of glucose-stimulated insulin secretion (GSIS), which worsens as glucose levels climb. Toxic effects of glucose on β cells (glucotoxicity) appear to be the culprit. This dysfunctional insulin secretion can be reversed when glucose levels are lowered by treatment, a finding with therapeutic significance. Restoration of β cell mass in both types of diabetes could be accomplished by either β cell regeneration or transplantation. Learning more about the relationships between β cell mass, turnover, and function and finding ways to restore β cell mass are among the most urgent priorities for diabetes research

Somatostatin: Diverse Physiological Roles and Therapeutic Implications

In its brief lifetime as a known peptide, somatostatin has provided a truly remarkable story filled with surprising developments from unexpected quarters. The foundation was set in 1969, when Krulich and McCann reported that fractions of a crude hypothalamic extract inhibited the secretion of growth hormone. In 1973, Guillemin\u27s laboratory reported the sequence and synthesis of a fourteen amino acid peptide with the same inhibitory effect. It occurs in both a cyclic and linear form, each displaying equal biological activity. Somatostatin was assigned as its name, but it is also commonly referred to as growth hormone release inhibitory factor (GHRIF) or somatotropin-release inhibiting factor (SRIF)

β-cell dedifferentiation in diabetes is important, but what is it?

This commentary discusses the concept of β-cell dedifferentiation in diabetes, which is important but not well defined. A broad interpretation is that a state of differentiation has been lost, which means changes in gene expression as well as in structural and functional elements. Thus, a fully mature healthy β cell will have its unique differentiation characteristics, but maturing cells and old β cells will have different patterns of gene expression and might therefore be considered as dedifferentiated. The meaning of dedifferentiation is now being debated because β cells in the diabetic state lose components of their differentiated state, which results in severe dysfunction of insulin secretion. The major cause of this change is thought to be glucose toxicity (glucotoxicity) and that lowering glucose levels with treatment results in some restoration of function. An issue to be discussed is whether dedifferentiated β cells return to a multipotent precursor cell phenotype or whether they follow a different pathway of dedifferentiation

Stem cell approaches for diabetes: towards beta cell replacement

Stem cells hold great promise for pancreatic beta cell replacement therapy for diabetes. In type 1 diabetes, beta cells are mostly destroyed, and in type 2 diabetes beta cell numbers are reduced by 40% to 60%. The proof-of-principle that cellular transplants of pancreatic islets, which contain insulin-secreting beta cells, can reverse the hyperglycemia of type 1 diabetes has been established, and there is now a need to find an adequate source of islet cells. Human embryonic stem cells can be directed to become fully developed beta cells and there is expectation that induced pluripotent stem (iPS) cells can be similarly directed. iPS cells can also be generated from patients with diabetes to allow studies of the genomics and pathogenesis of the disease. Some alternative approaches for replacing beta cells include finding ways to enhance the replication of existing beta cells, stimulating neogenesis (the formation of new islets in postnatal life), and reprogramming of pancreatic exocrine cells to insulin-producing cells. Stem-cell-based approaches could also be used for modulation of the immune system in type 1 diabetes, or to address the problems of obesity and insulin resistance in type 2 diabetes. Herein, we review recent advances in our understanding of diabetes and beta cell biology at the genomic level, and we discuss how stem-cell-based approaches might be used for replacing beta cells and for treating diabetes

Islets in Type 2 Diabetes: In Honor of Dr. Robert C. Turner

long as the work is properly cited, the use is educational and not for profit, and the work is not altered. Se

Induction of remission in diabetes by lowering blood glucose

As diabetes continues to grow as major health problem, there has been great progress in understanding the important role of pancreatic beta-cells in its pathogenesis. Diabetes develops when the normal interplay between insulin secretion and the insulin sensitivity of target tissues is disrupted. With type 2 diabetes (T2D), glucose levels start to rise when beta-cells are unable to meet the demands of insulin resistance. For type 1 diabetes (T1D) glucose levels rise as beta-cells are killed off by autoimmunity. In both cases the increased glucose levels have a toxic effect on beta-cells. This process, called glucose toxicity, has a major inhibitory effect on insulin secretion. This beta-cell dysfunction can be reversed by therapies that reduce glucose levels. Thus, it is becoming increasingly apparent that an opportunity exists to produce a complete or partial remission for T2D, both of which will provide health benefit

Transplanted Beta Cell Response to Increased Metabolic Demand Changes in Beta Cell Replication and Mass

Abstract We determined the capacity of transplanted beta cells to modify their replication and mass when stimulated by changes in metabolic demand. Invest. 1994Invest. . 93:1577Invest. -158

Medicines Conversation Guide

A Medicines Conversation Guide was developed for pharmacists to use in the context of a Home Medicines Review. The Guide aims to increase patient involvement and support discussions about: general health understanding, decision-making and information preferences, health priorities related to medicines, patient goals and fears, views on important activities and trade-offs