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The pancreatic islets comprising only 1%-2% of the volume are highly vascularized and innervated mini-organs. They contain five endocrine cell types, including β cells that secrete insulin, which is synthesized as a single polypeptide chain, preproinsulin, processed to proinsulin, and finally to insulin and C-peptide. This process is complex and regulated, involving the Golgi complex, the endoplasmic reticulum, and the secretory granules of the β cell.
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Insulin secretory vesicles release insulin to stimulate blood glucose uptake and regulate carbohydrate metabolism. When the blood glucose levels increase, glucose enters the pancreatic β-islet cells through glucose transporters. Once inside, glucose is metabolized through glycolysis, the citric acid cycle, and the electron transport chain, producing ATP. This increase in ATP concentration closes ATP-sensitive potassium channels, leading to depolarization of the membrane and the opening of...
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Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
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Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but...
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Insulin-replacement therapy usually includes both long-acting insulin (basal) and short-acting insulin (to cater to postprandial needs). In a diverse group of type 1 diabetes patients, the average daily insulin dose is typically 0.5-0.7 units/kg body weight. However, obese patients and pubertal adolescents may need more due to insulin resistance.
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Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a...
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Updated: Jul 27, 2025

Homogeneous Time-resolved Förster Resonance Energy Transfer-based Assay for Detection of Insulin Secretion
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Asiatic acid improves insulin secretion of

Lu Li1, Wei Wang2, Qiang Xu3

  • 1Department of Clinical Pharmacy, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China. lucille@zju.edu.cn.

Zhejiang Da Xue Xue Bao. Yi Xue Ban = Journal of Zhejiang University. Medical Sciences
|June 7, 2023
PubMed
Summary

Asiatic acid enhances pancreatic beta-cell function and insulin secretion in type 2 diabetes by maintaining beta-cell maturity. This may involve the TNF-alpha/Mfn2 pathway, improving glycemic control.

Keywords:
Asiatic acidGlucose stimulated insulin secretionInflammatory factorMouseType 2 diabetesβ cells

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Area of Science:

  • Endocrinology
  • Pharmacology
  • Metabolic Diseases

Background:

  • Type 2 diabetes mellitus (T2DM) is characterized by impaired beta-cell function.
  • Understanding molecular mechanisms to improve beta-cell function is crucial for T2DM treatment.

Purpose of the Study:

  • To investigate the effects of asiatic acid on beta-cell function in T2DM.
  • To elucidate the molecular mechanisms underlying asiatic acid's action.

Main Methods:

  • A T2DM mouse model was established using high-fat diet and streptozotocin.
  • Assays included ELISA for insulin secretion and inflammatory markers, ATP production measurement, and Western blotting for protein expression (Mfn2, Ucn3).
  • siRNA interference and TNF-alpha treatment were used to explore molecular pathways.

Main Results:

  • Asiatic acid (25 mg·kg－1·d－1) improved glycemic control and beta-cell function in T2DM mice.
  • It enhanced glucose-stimulated insulin secretion (GSIS), ATP production, and expression of Mfn2 and Ucn3.
  • siRNA-mediated Mfn2 interference blocked asiatic acid's beneficial effects; asiatic acid counteracted TNF-alpha-induced inhibition.

Conclusions:

  • Asiatic acid improves beta-cell insulin secretion in T2DM by maintaining beta-cell maturity.
  • The mechanism may involve the TNF-alpha/Mfn2 signaling pathway.