Genotrophic effect of neurotrophins - Restart of β-cell regeneration in diabetes mellitus

Med Hypotheses. 2017 Sep:107:9-11. doi: 10.1016/j.mehy.2017.06.025. Epub 2017 Jun 29.

Abstract

Type 2 diabetes mellitus is an epidemic worldwide and a proved risk factor for cardiovascular complications. In 89% of the cases, it deals, in fact, with metabolic syndrome of multifactorial etiopathogenesis. This paradigm has been generalized by the neurotrophic theory emphasizing the role of hyponeurotrophinemia of key factor. Both type 2 diabetes mellitus and metabolic syndrome are characterized by insulin resistance and pancreatic β-cell damage. Cyclic keeping the fast enhances plasma neurotrophin levels. Fasting induces prenatal-development gene expression in adult pancreas and promotes neurogenin (Ngn)-3 gene expression to generate insulin producing β-cells. Probably, the increased plasma and tissue levels of the nerve growth factor and brain-derived neurotrophic factor after fasting reprogramme Ngn-3 gene expression as this genotrophic action enhances Ngn-3 protein synthesis. This results in regeneration of damaged pancreatic β-cells and restores insulin secretion in type 1 and type 2 diabetes mellitus.

Keywords: Brain-derived neurotrophic factor; Diabetes mellitus; Nerve growth factor; β-Cell regeneration.

MeSH terms

  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / physiology
  • Brain-Derived Neurotrophic Factor / physiology
  • Diabetes Mellitus / genetics
  • Diabetes Mellitus / physiopathology*
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / physiopathology
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / physiopathology
  • Fasting / physiology
  • Gene Expression
  • Humans
  • Insulin / metabolism
  • Insulin Secretion
  • Insulin-Secreting Cells / physiology*
  • Metabolic Syndrome / genetics
  • Metabolic Syndrome / physiopathology
  • Models, Biological
  • Nerve Growth Factor / physiology
  • Nerve Growth Factors / genetics
  • Nerve Growth Factors / physiology*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology
  • Regeneration / genetics
  • Regeneration / physiology*

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Brain-Derived Neurotrophic Factor
  • Insulin
  • NEUROG3 protein, human
  • Nerve Growth Factors
  • Nerve Tissue Proteins
  • BDNF protein, human
  • Nerve Growth Factor