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Clinical Approaches to Preserve β-Cell Function in Diabetes

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Book cover The Islets of Langerhans

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 654))

Abstract

In type 2 diabetes (DM2) there is progressive deterioration in β-cell function and mass. It was found that islet function was about 50% of normal at the time of diagnosis and reduction in β-cell mass of about 60% at necropsy (accelerated apoptosis). Among the interventions to preserve the β-cells, those to lead to short-term improvement of β-cell secretion are weight loss, metformin, sulfonylureas, and insulin. The long-term improvement was demonstrated with short-term intensive insulin therapy of newly diagnosed DM2, the use of antiapoptotic drugs such as glitazones, and the use of glucagon-like peptide-1 receptor agonists (GLP-1 mimetics), not inactivated by the enzyme dipeptidyl peptidase 4 and/or to inhibit that enzyme (GLP-1 enhancers). The incretin hormones are released from the gastrointestinal tract in response to nutrient ingestion to enhance glucose-dependent insulin secretion from the pancreas and overall maintenance of glucose homeostasis. From the two major incretins, GLP-1 and GIP (glucose-dependent insulinotropic polypeptide), only the first one or its mimetics or enhancers can be used for treatment. The GLP-1 mimetics exenatide and liraglutide as well as the DPP 4 inhibitors (sitagliptin and vildagliptin) were approved for treatment of DM2.

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Abbreviations

AST:

Aspartate amino transferase

ALT:

alanine amino transferase

BMI:

body mass index

DM2:

type 2 diabetes mellitus

DPP4:

dipeptidyl peptidase 4

ER:

endoplasmic reticulum

FA:

fatty acid

FFA:

free fatty acid

GIP:

glucose-dependent insulinotropic polypeptide

GLP-1:

glucagon-like peptide-1

GLP-1R:

glucagon-like peptide-1 receptor

GLP-2:

glucagon-like peptide-2

HbA1c:

glycated hemoglobin

HOMA:

homeostasis model assessment

HOMA-βorB:

HOMA of β-cell function

IFG:

impaired fasting glucose

IGT:

impaired glucose tolerance

PI/IRIratio:

proinsulin to total immunoreactive insulin ratio

PPARγ:

peroxisome proliferator-activated receptor γ

ROS:

reactive oxygen species

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Authors and Affiliations

  1. Endocrine Service and Diabetes and Heart Center of the Heart Institute, Hospital das, Clinicas of The University of São Paulo Medical School, São Paulo, SP 05403-000, Brazil

    Bernardo Léo Wajchenberg

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  1. Dept. Clinical Research & Education, Karolinska Institutet, Stockholm, 118 83, Sweden

    Md. Shahidul Islam

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Wajchenberg, B.L. (2010). Clinical Approaches to Preserve β-Cell Function in Diabetes. In: Islam, M. (eds) The Islets of Langerhans. Advances in Experimental Medicine and Biology, vol 654. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-3271-3_23

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