Diabetes Metab J.  2014 Dec;38(6):426-436. 10.4093/dmj.2014.38.6.426.

Therapeutic Approaches for Preserving or Restoring Pancreatic beta-Cell Function and Mass

• Jung KY
• Kim KM
• Lim S

• KMID: 2174079
• DOI: http://doi.org/10.4093/dmj.2014.38.6.426

Abstract

The goal for the treatment of patients with diabetes has today shifted from merely reducing glucose concentrations to preventing the natural decline in beta-cell function and delay the progression of disease. Pancreatic beta-cell dysfunction and decreased beta-cell mass are crucial in the development of diabetes. The beta-cell defects are the main pathogenesis in patients with type 1 diabetes and are associated with type 2 diabetes as the disease progresses. Recent studies suggest that human pancreatic beta-cells have a capacity for increased proliferation according to increased demands for insulin. In humans, beta-cell mass has been shown to increase in patients showing insulin-resistance states such as obesity or in pregnancy. This capacity might be useful for identifying new therapeutic strategies to reestablish a functional beta-cell mass. In this context, therapeutic approaches designed to increase beta-cell mass might prove a significant way to manage diabetes and prevent its progression. This review describes the various beta-cell defects that appear in patients with diabetes and outline the mechanisms of beta-cell failure. We also review common methods for assessing beta-cell function and mass and methodological limitations in vivo. Finally, we discuss the current therapeutic approaches to improve beta-cell function and increase beta-cell mass.

Keyword

beta-Cell function; beta-Cell mass; Therapeutic agents

MeSH Terms

Glucose
Humans
Insulin
Obesity
Pregnancy
Glucose
Insulin

Figure

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  Fig. 1 Regulation of the pancreatic β-cell mass dynamics.

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  Fig. 2 Regulation of the pancreatic β-cell by peroxisome proliferator-activated receptor-gamma (PPARγ). RXR, retinoid X receptor; GLP-1R, glucagon-like peptide-1R; PI3K, phosphatidylinositol-3 kinase; IRS, insulin receptor substrate; PDX-1, pancreas duodenum homeobox-1; GLUT2, glucose transporter 2.

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  Fig. 3 Regulation of the pancreatic β-cell by glucagon-like peptide-1 (GLP-1). GLUT2, glucose transporter 2; K-ATP, ATP-sensitive potassium channel; TCA, tricarboxylic acid; EGFR, epidermal growth factor receptor; VDCC, voltage-dependent calcium channels; PI3K, phosphatidylinositol-3 kinase; IRS, insulin receptor substrate; PKC, protein kinase C; MAPK, mitogen-activated protein kinase; ER, endoplasmic reticulum; cAMP, cyclic adenosine monophosphate; PKA, protein kinase A; AC, adenylate cyclase; Epac, exchange protein activated by cAMP.

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  Fig. 4 Insulin-induced inactivation of glycogen synthase kinase 3 β (GSK3β). IRS, insulin receptor substrate; PI3K, phosphatidylinositol-3 kinase.

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  Fig. 5 Regulation of the pancreatic β-cell by G protein-coupled receptor 40 (GPR40). GLUT2, glucose transporter 2; K-ATP, ATP-sensitive potassium channel; TCA, tricarboxylic acid; VDCC, voltage-dependent calcium channels; PLC, phospholipase C; DAG, diacylglycerol; PKC, protein kinase C; IP3, 1,4,5-trisphosphate; PIP2, 4,5-bisphosphate; ER, endoplasmic reticulum; cAMP, cyclic adenosine monophosphate; PKA, protein kinase A; Epac, exchange protein activated by cAMP; AC, adenylate cyclase; GLP-1, glucagon-like peptide-1.

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