Metformin mitigates impaired testicular lactate transport/utilisation and improves sexual behaviour in streptozotocin-induced diabetic rats

Arch Physiol Biochem. 2021 Feb;127(1):51-60. doi: 10.1080/13813455.2019.1610778. Epub 2019 May 10.

Abstract

Context: Lactate is the preferred energy substrate for developing testicular germ cells. Diabetes is associated with impaired testicular lactate transport/utilisation, and poor sexual behaviour.

Objective: To examine the effects of metformin on parameters involved in testicular lactate production, transport/utilisation, and sexual behaviour in diabetic state.

Methods: Male Sprague-Dawley rats were assigned into normal control (NC), diabetic control (DC), and metformin-treated diabetic group (n = 6/group). Metformin (300 mg/kg b.w./day) was administrated orally for 4 weeks.

Results: Intra-testicular glucose and lactate levels, and lactate dehydrogenase (LDH) activity increased, while the mRNA transcript levels of genes responsible for testicular glucose and lactate transport/utilisation (glucose transporter 3, monocarboxylate transporter 4 (MCT4), MCT2, and LDH type C) decreased in DC group. Furthermore, penile nitric oxide increased, while cyclic guanosine monophosphate decreased, with impaired sexual behaviour in DC group. Treatment with metformin improved these parameters.

Conclusions: Metformin increases testicular lactate transport/utilisation and improves sexual behaviour in diabetic state.

Keywords: Diabetes mellitus; lactate; metformin; monocarboxylate transporters; sexual behaviour.

MeSH terms

  • Animals
  • Biological Transport
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Glucose Tolerance Test
  • Glucose Transporter Type 1 / biosynthesis
  • Glucose Transporter Type 3 / biosynthesis
  • Hypoglycemic Agents / pharmacology
  • Insulin / blood
  • Lactic Acid / metabolism*
  • Male
  • Metformin / pharmacology*
  • Nitric Oxide / metabolism
  • Penis / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Sexual Behavior, Animal / drug effects*
  • Streptozocin
  • Testis / metabolism*

Substances

  • Glucose Transporter Type 1
  • Glucose Transporter Type 3
  • Hypoglycemic Agents
  • Insulin
  • Slc2a1 protein, rat
  • Slc2a3 protein, rat
  • Nitric Oxide
  • Lactic Acid
  • Streptozocin
  • Metformin