Increased insulin and GLUT2 gene expression and elevated glucokinase activity in β-like cells of islets of langerhans differentiated from human haematopoietic stem cells on treatment with Costus igneus leaf extract

Mol Biol Rep. 2021 May;48(5):4477-4485. doi: 10.1007/s11033-021-06467-x. Epub 2021 Jun 9.

Abstract

In the quest to understand lost β-cells regeneration in the diabetic condition, we have demonstrated successful differentiation of human haematopoietic stem cells (HSCs) to functional β-like cells. Costus igneus (Ci) leaf extract is known to exhibit anti-diabetic properties by lowering the blood glucose level as demonstrated in mice models. To establish the anti-diabetic properties of Ci leaf extract on human subjects, we studied the effect of Ci on these differentiated β-like cells. Ci leaf extract showed its anti-diabetic property through elevated glucokinase activity which catalyzes the rate-limiting step of glucose catabolism in β-like cells and acts as a sensor for insulin production while decreasing the glucose-6-phosphatase activity. Upon increasing the concentrations of Ci leaf extract (25, 65, 105, 145, 185 µg/ml) and glucose concentrations (5.5, 11.1, and 25 mM) Ci leaf extract treated β-like cells showed enhanced glucokinase and decreased glucose-6-phosphatase activities and an exponential rise in gene expressions of INS and GLUT2 was observed. The present study shows enhanced INS and GLUT2 gene expression and elevated glucokinase activity in β-like cells differentiated from HSCs upon treatment with Ci leaf extract explain the anti-diabetic property of Ci leaf extract. This extract can be effectively used in the management of diabetes.

Keywords: Anti-diabetic property; Costus igneus; Human Haematopoietic stem cells; In vitro differentiated β-like cells.

MeSH terms

  • Blood Donors
  • Cell Differentiation / drug effects*
  • Cells, Cultured
  • Costus / chemistry*
  • Gene Expression / drug effects*
  • Glucokinase / metabolism*
  • Glucose / metabolism
  • Glucose Transporter Type 2 / genetics*
  • Glucose-6-Phosphatase / metabolism
  • Healthy Volunteers
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / drug effects
  • Humans
  • Hypoglycemic Agents / pharmacology*
  • Insulin / genetics*
  • Insulin-Secreting Cells / enzymology*
  • Plant Extracts / pharmacology*
  • Plant Leaves / chemistry*
  • Signal Transduction / drug effects*

Substances

  • Glucose Transporter Type 2
  • Hypoglycemic Agents
  • Insulin
  • Plant Extracts
  • SLC2A2 protein, human
  • Glucokinase
  • Glucose-6-Phosphatase
  • Glucose