Related Experiment Video

Updated: Jan 1, 2026

Biosynthesis of a Flavonol from a Flavanone by Establishing a One-pot Bienzymatic Cascade
09:50

Biosynthesis of a Flavonol from a Flavanone by Establishing a One-pot Bienzymatic Cascade

Published on: August 14, 2019

9.7K

Flavonoid derivatives synthesis and anti-diabetic activities

Ying Chen1, Feng-Bo Cheng1, Xiao-Ran Wu1

  • 1School of Pharmacy, Tianjin Medical University, Tianjin Key Laboratory on Technologies Enabling Development Clinical Therapeutics and Diagnostics (Theragnostic), Tianjin, People's Republic of China.

Bioorganic Chemistry
|December 23, 2019
PubMed

Insights

A new compound, 10b, derived from Fla-CN, shows potent anti-diabetic effects by improving glucose consumption and insulin sensitivity. This discovery offers a promising avenue for developing novel anti-diabetic medications.

Area of Science:

  • Biochemistry
  • Pharmacology
  • Metabolic Diseases

Background:

  • Tiliroside derivative Fla-CN exhibits anti-diabetic and anti-obesity properties in obese mice.
  • Insulin resistance (IR) is a key factor in metabolic disorders like type 2 diabetes.

Purpose of the Study:

  • To optimize Fla-CN and evaluate a new derivative, 10b, for its efficacy in improving glucose metabolism.
  • To elucidate the molecular mechanisms underlying 10b's effects in insulin-resistant cells.

Main Methods:

  • Hepatocellular carcinoma G2 (HepG2) cells were used to assess glucose consumption and glycogen content.
  • Western blotting was employed to analyze the phosphorylation of key signaling proteins and the expression of gluconeogenic enzymes.

Main Results:

  • 10b demonstrated significant glucose consumption in IR HepG2 cells at nanomolar concentrations (EC50 = 0.3 nM).
  • 10b increased glycogen synthesis and glucose uptake while inhibiting gluconeogenesis.
  • 10b enhanced the phosphorylation of AMP-activated protein kinase (AMPK) and AS160, and reduced phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6P) levels.

Conclusions:

  • 10b effectively improves glucose metabolism in insulin-resistant cells.
  • The mechanism involves the activation of AMPK/AS160 and AMPK/PEPCK/G6P pathways.
  • 10b represents a promising candidate for the development of new anti-diabetic drugs.
Keywords:
AMPK pathwayFlavonoidsGlucose metabolism disordersRatio of AMP/ATPStructure-activity relationship

More Related Videos

Screening and Isolation of C-Glycoside-Cleaving Intestinal Bacteria06:38

Screening and Isolation of C-Glycoside-Cleaving Intestinal Bacteria

Published on: February 28, 2025

628
An In Ovo Model for Testing Insulin-mimetic Compounds06:09

An In Ovo Model for Testing Insulin-mimetic Compounds

Published on: April 23, 2018

11.0K

Related Concept Videos

Oral Hypoglycemic Agents: Biguanides and Glitazones01:26

Oral Hypoglycemic Agents: Biguanides and Glitazones

Biguanides, particularly metformin (Glucophage), are insulin sensitizers that enhance glucose uptake, thereby reducing insulin resistance. Unlike sulfonylureas, metformin doesn't prompt insulin secretion, which helps to curb hypoglycemia risk. Metformin is beneficial in treating conditions like polycystic ovary syndrome due to its insulin-resistance reduction capability. The drug's primary action involves curtailing hepatic gluconeogenesis, a significant contributor to high blood...
542
Oral Hypoglycemic Agents: Sulfonylureas01:17

Oral Hypoglycemic Agents: Sulfonylureas

Sulfonylureas are oral hypoglycemic agents utilized in treating type 2 diabetes. They are characterized by their unique sulfonylurea chemical structure. The family of sulfonylureas is divided into generations. First-generation sulfonylureas, including tolbutamide (Orinase), chlorpropamide (Diabinese), and tolazamide (Tolinase), trigger insulin release from pancreatic β cells and enhance peripheral tissues' insulin sensitivity. The second-generation members, such as glipizide...
682
Oral Hypoglycemic Agents: Glinides01:06

Oral Hypoglycemic Agents: Glinides

Repaglinide (Prandin) and Nateglinide (Starlix), known as glinides, are oral insulin secretagogues that stimulate insulin release from pancreatic β cells by closing the ATP-sensitive potassium channels (KATP channel). Repaglinide controls insulin release from pancreatic β cells by managing potassium efflux. It shares two binding sites with sulfonylureas and also has a unique site, indicating overlapping mechanisms of action. With a rapid onset and a 4-7 hour duration, it effectively...
531
Oral Hypoglycemic Agents: α-Glucosidase Inhibitors01:19

Oral Hypoglycemic Agents: α-Glucosidase Inhibitors

α-glucosidase inhibitors, including acarbose (Precose), miglitol (Glyset), and voglibose (Voglib) (primarily available in Asia), are drugs that control blood sugar levels by delaying the digestion of starch and disaccharides. They achieve this by inhibiting α-glucosidase enzymes in the intestine, which slow the absorption of carbohydrates in the intestine, which in turn leads to a prolonged release of the glucoregulatory hormone GLP-1 from intestinal L-cells.
Acarbose and miglitol are...
481
Dipeptidyl Peptidase 4 Inhibitors01:23

Dipeptidyl Peptidase 4 Inhibitors

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...
519
Glucagon-like Receptor Agonists01:24

Glucagon-like Receptor Agonists

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.
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...
783