Related Experiment Video

Updated: Nov 2, 2025

Studying Pancreatic Cancer Stem Cell Characteristics for Developing New Treatment Strategies
07:29

Studying Pancreatic Cancer Stem Cell Characteristics for Developing New Treatment Strategies

Published on: June 20, 2015

19.8K

Metformin Reduces Vascular Assembly in High Glucose-Treated Human Microvascular Endothelial Cells in An

Carolina Silva1,2, Ilda Rodrigues1, Sara Andrade1,2,3

  • 1Department of Biomedicine, Unit of Biochemistry, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal.

Cell Journal
|June 7, 2021
PubMed
Abstract

Insights

Metformin inhibits human microvascular endothelial cell (HMEC) vessel formation and migration, likely via an AMP-independent pathway. This finding is crucial for understanding endothelial dysfunction and preventing diabetic complications.

Area of Science:

  • Endothelial cell biology
  • Diabetic complications research
  • Pharmacological effects on angiogenesis

Background:

  • High glucose (HG) conditions induce endothelial dysfunction, a key factor in diabetic microvascular complications.
  • 5' adenosine monophosphate-activated protein kinase (AMPK) modulators are investigated for their therapeutic potential in managing diabetic complications.
  • Metformin's effects on endothelial cells under hyperglycemic conditions require further elucidation.

Purpose of the Study:

  • To investigate the impact of metformin on human microvascular endothelial cells (HMECs) exposed to high glucose (HG).
  • To compare metformin's effects with other 5' adenosine monophosphate-activated protein kinase (AMPK) modulators under HG conditions.
  • To assess the influence of metformin on HMEC migration, invasion, proliferation, and capillary-like structure formation.

Main Methods:

  • Human microvascular endothelial cells (HMECs) were treated with metformin, AICAR, and compound C under high glucose (20 mM) conditions.
  • Cellular functions including migration, invasion, and proliferation were evaluated.
  • Capillary-like structure formation and the expression of angiogenic genes were assessed.

Main Results:

  • Metformin significantly inhibited HMEC migration and vessel formation but did not affect proliferation or invasion.
  • Histological analysis showed metformin reduced collagen formation.
  • Gene expression analysis revealed slight upregulation of angiogenesis and fibrosis-related genes (e.g., TGFß2, VEGFR2, SMADs) and differential SMAD2/3 expression.

Conclusions:

  • Metformin prevents vessel assembly in HMECs, potentially through an AMPK-independent mechanism.
  • Understanding metformin's molecular effects on endothelial dysfunction is vital for its application in diabetic retinopathy and nephropathy.
  • These findings highlight metformin's potential role in managing angiogenesis-related complications in diabetes.
Keywords:
AICARAMPK SignalingCompound CEndothelial CellsMetformin

More Related Videos

Measurement of Insulin- and Contraction-Stimulated Glucose Uptake in Isolated and Incubated Mature Skeletal Muscle from Mice08:01

Measurement of Insulin- and Contraction-Stimulated Glucose Uptake in Isolated and Incubated Mature Skeletal Muscle from Mice

Published on: May 16, 2021

6.2K
Isolation of Primary Mouse Hepatocytes for Nascent Protein Synthesis Analysis by Non-radioactive L-azidohomoalanine Labeling Method08:04

Isolation of Primary Mouse Hepatocytes for Nascent Protein Synthesis Analysis by Non-radioactive L-azidohomoalanine Labeling Method

Published on: October 23, 2018

19.3K

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...
378
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...
314
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
7.1K
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...
345
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
4.3K
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...
1.6K