Related Experiment Video

Updated: Nov 30, 2025

Author Spotlight: Unraveling Vitamin A Transport Mechanisms — Linking Liver Receptors to Vision Health Through RBPR2 and RBP4 Interactions
08:18

Author Spotlight: Unraveling Vitamin A Transport Mechanisms — Linking Liver Receptors to Vision Health Through RBPR2 and RBP4 Interactions

Published on: October 4, 2024

1.4K

Retinol-Binding Protein 4 Activates STRA6, Provoking Pancreatic β-Cell Dysfunction in Type 2 Diabetes

Rong Huang1, Xinxiu Bai1, Xueyan Li2

  • 1Guangdong Provincial Key Laboratory of Food, Nutrition, and Health and Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, Guangdong Province, People's Republic of China.

Diabetes
|November 17, 2020
PubMed

Insights

Retinol-binding protein 4 (RBP4) impairs pancreatic beta-cell function and insulin secretion in type 2 diabetes. Reducing RBP4 levels can restore beta-cell function and improve hyperglycemia.

Area of Science:

  • Endocrinology
  • Metabolic Diseases
  • Cell Biology

Background:

  • Pancreatic beta-cell dysfunction is central to type 2 diabetes progression.
  • Retinol-binding protein 4 (RBP4) is an adipokine implicated in type 2 diabetes, but its direct impact on beta-cells and mechanisms are unclear.

Purpose of the Study:

  • To investigate the role of RBP4 in pancreatic beta-cell function and insulin secretion.
  • To elucidate the molecular mechanisms by which RBP4 affects beta-cells.

Main Methods:

  • Correlational analysis of circulating RBP4 levels and beta-cell function in db/db mice.
  • In vitro studies using isolated islets and INS-1E cells to assess RBP4's effect on glucose-stimulated insulin secretion (GSIS).
  • Analysis of RBP4 transgenic (RBP4-Tg) mice and investigation of the STRA6/JAK2/STAT1/ISL-1 pathway.

Main Results:

  • Elevated RBP4 levels inversely correlated with beta-cell function in db/db mice.
  • RBP4 directly suppressed GSIS in a dose- and time-dependent manner.
  • RBP4-Tg mice exhibited decreased GSIS early in development, preceding insulin resistance; STRA6 mediated RBP4's inhibitory effect on insulin synthesis via the JAK2/STAT1/ISL-1 pathway.

Conclusions:

  • RBP4 directly impairs pancreatic beta-cell function and insulin secretion.
  • The STRA6 receptor mediates RBP4's inhibitory effects on beta-cells through the JAK2/STAT1/ISL-1 pathway.
  • Reducing circulating RBP4 levels offers a potential therapeutic strategy for restoring beta-cell function and ameliorating hyperglycemia in type 2 diabetes.

More Related Videos

Author Spotlight: Investigating Physiological Functions of Vitamin A Transporters Using HPLC-Based Vitamin A Profiling05:03

Author Spotlight: Investigating Physiological Functions of Vitamin A Transporters Using HPLC-Based Vitamin A Profiling

Published on: December 27, 2024

1.5K
A High-content In Vitro Pancreatic Islet β-cell Replication Discovery Platform09:35

A High-content In Vitro Pancreatic Islet β-cell Replication Discovery Platform

Published on: July 16, 2016

11.5K

Related Concept Videos

Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
15.1K
Insulin Secretory Vesicles01:05

Insulin Secretory Vesicles

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...
6.2K
Insulin: The Receptor and Signaling Pathways01:28

Insulin: The Receptor and Signaling Pathways

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...
2.1K
Hormones Regulating Blood Glucose01:16

Hormones Regulating Blood Glucose

Insulin is released by beta cells of the pancreas when blood glucose levels are high. It facilitates glucose absorption and utilization in insulin-dependent cells with insulin receptors on their plasma membranes. Insulin promotes glucose uptake by increasing the number of glucose transport proteins in the cell membrane, allowing glucose to enter the cell. As a result, glucose utilization and ATP production are enhanced.
In addition to accelerating glucose uptake and utilization, insulin has...
5.8K
Insulin: Biosynthesis, Chemistry, and Preparation01:25

Insulin: Biosynthesis, Chemistry, and Preparation

The endoplasmic reticulum (ER) of pancreatic β-cells synthesizes preproinsulin, which consists of a signal peptide, A and B chains, and a C-peptide. Preproinsulin is then cleaved and folded into proinsulin, which translocates to the Golgi apparatus for sorting and packaging into secretory granules. In these granules, enzymatic clipping generates insulin and C-peptide.
Damage or functional impairment of β-cells inhibits insulin production, leading to diabetes. Diabetes treatment...
907
Glucose Homeostasis: Pancreatic Islets and Insulin Secretion01:27

Glucose Homeostasis: Pancreatic Islets and Insulin Secretion

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.
Insulin and C-peptide are...
1.8K