Related Experiment Video
Updated: Jun 25, 2025
Study of In Vivo Glucose Metabolism in High-fat Diet-fed Mice Using Oral Glucose Tolerance Test OGTT and Insulin Tolerance Test ITT
Published on: January 7, 2018
Potential of FGF21 in type 2 diabetes mellitus treatment based on untargeted metabolomics
Shuai Li1, Zilong Song2, Chunxiang Fan2
1College of Life Sciences and Agriculture and Forestry, Qiqihar University, Qiqihar 161006, China; State Key Laboratory of New-Tech for Chinese Medicine Pharmaceutical Process, Jiangsu Kanion Parmaceutical CO. LTD, Lianyungang 222001, People s Republic of China.
Abstract:
Fibroblast growth factor 21 (FGF21) has promise for treating diabetes and its associated comorbidities. It has been found to reduce blood glucose in mice and humans; however, its underlying mechanism is not known. Here, the metabolic function of FGF21 in diabetes was investigated. Diabetic db/db mice received intraperitoneal injections of FGF21 for 28 days, the serum of each mouse was collected, and their metabolites were analyzed by untargeted metabolomics using UHPLC-MS/MS. It was found that FGF21 reduced blood glucose and oral glucose tolerance without causing hypoglycemia. Moreover, administration of FGF21 reduced the levels of TG and LDL levels while increasing those of HDL and adiponectin. Importantly, the levels of 45 metabolites, including amino acids and lipids, were significantly altered, suggesting their potential as biomarkers. We speculated that FGF21 may treat T2DM through the regulation of fatty acid biosynthesis, the TCA cycle, and vitamin digestion and absorption. These findings provide insight into the mechanism of FGF21 in diabetes and suggest its potential for treating diabetes.
Insights
Fibroblast growth factor 21 (FGF21) effectively lowers blood glucose and improves lipid profiles in diabetic mice. This study reveals FGF21
Area of Science:
- Endocrinology
- Metabolomics
- Biochemistry
Background:
- Fibroblast growth factor 21 (FGF21) shows therapeutic potential for type 2 diabetes mellitus (T2DM) and related conditions.
- The precise metabolic mechanisms underlying FGF21's glucose-lowering effects remain largely unelucidated.
Purpose of the Study:
- To investigate the metabolic functions and mechanisms of FGF21 in a mouse model of diabetes.
- To identify potential metabolic biomarkers associated with FGF21 treatment.
Main Methods:
- Administration of FGF21 via intraperitoneal injections to diabetic db/db mice over 28 days.
- Untargeted metabolomic analysis of serum samples using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS).
Main Results:
- FGF21 significantly reduced blood glucose and improved oral glucose tolerance without inducing hypoglycemia.
- Treatment with FGF21 led to decreased triglyceride (TG) and low-density lipoprotein (LDL) levels, alongside increased high-density lipoprotein (HDL) and adiponectin levels.
- Alterations in 45 metabolites, including amino acids and lipids, were observed, suggesting their utility as potential biomarkers.
Conclusions:
- FGF21 demonstrates efficacy in improving glycemic control and lipid profiles in a diabetic mouse model.
- Metabolomic analysis suggests FGF21 may exert its therapeutic effects by modulating fatty acid biosynthesis, the tricarboxylic acid (TCA) cycle, and vitamin digestion and absorption pathways.
- These findings provide critical insights into FGF21's mechanism of action in T2DM and highlight its therapeutic promise.
Related Concept Videos
01:22Diabetes Mellitus: Type 2 and Gestational
01:15Diabetes: Management and Pharmacotherapy
Insulin remains the cornerstone of treatment for most patients with type 1 and many...
01:36Carbohydrate Metabolism
Starch accounts for approximately 60% of the carbohydrates consumed by humans. Since amylase enzymes cannot function in the stomach's acidic environment, starch can only be digested in the mouth and small intestine. Simple sugars are found naturally in milk and fruits in...
01:22Diabetes Mellitus: Overview and Type I Subtype
Type 1 diabetes is an autoimmune disease in which the immune system mistakenly attacks and destroys the insulin-producing beta cells in the pancreas. As a result, the body is unable to produce sufficient insulin, and individuals with...
01:24Glucagon-like Receptor Agonists
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
01:20Pathophysiology of Diabetes
Type 1 diabetes is characterized by autoimmune-mediated destruction of pancreatic β cells, with environmental factors potentially triggering this process in genetically susceptible individuals. Despite many not having a family history, certain genes increase susceptibility,...