Glucose transporters and PKC

Y Coleman,

21st October 2024

Examples of PharmacoNutrition ie some common blood tests impacted by some commonly prescribed medicines

​PKC mechanisms and consequences

PKC (Protein Kinase C) is a second pathway that stimulates insulin-dependent glucose transporters to translocate.

Outlined below are the key factors in both the insulin/IR/IRS/PI3K/PDK/Akt/GLUT and insulin/IR/PKS/GLUT pathways.

Image of the PKC_GLUT pathway in our MedNut Mail article Glucose transporters and PKC

PKC

PKC is present in every cell and is important in a range of physiological functions. The focus of this article is the role of PKC in stimulating insulin-dependent glucose transporter translocation.

PKC may be either a sole factor or one of several factors that influence the translocation stimulation for these insulin-dependent glucose transporters.

Transporter

PKC mechanism of action

GLUT1

for activation.

GLUT4

can stimulate translocation.

GLUT8

can stimulate translocation (bovine).

GLUT13

can stimulate translocation.

SGLT1

as a regulatory factor.

SGLT2

as a regulatory factor.

PKC’s activation and inhibition are dependent upon a range of normal and abnormal stressors, several of which seem to be related to DAG availability.

DAG (Diacylglyerol)

Either directly or indirectly, DAG is important in a range of functions that includes regulating the PKCs.

DAG is produced from either –

  • phosphatidylinositol 4,5- bisphosphate [PIP2] and phosphatidylcholine; or
  • dephosphorylation of phosphatidic acid (PA).

DGK (diacylglycerol kinase) regulates DAG levels. Decreased DGK activity means increased DAG and consequent PKC pathway stimulation.

One of DGK’s regulatory mechanisms is activation of the conversion of DAG to phosphatidic acid. This PA-DAG conversion reduces the availability of DAG and by default lowers PKC levels.

PKC activators

Phosphorylation of the tyrosine residues on IRS1 activates the PI3K/Akt/GLUT cascade. Phosphorylation of the serine 307 residues on IRS1 in skeletal muscle by PKC stimulates the insulin-dependent glucose transporters to translocate by an alternate pathway. Factors that activate PKC include –

Activators

PKC activation mechanisms of action

DAG

increased DAG levels.

high fat diets

increase DAG levels.

hyperglycaemia

increases the synthesis and accumulation of DAG from glucose.

Insulin resistance

stimulates the conversion of PIP2 to DAG (instead of converting PIP2 to PIP3).

Activated PKC inhibitors

Factors that inhibit activated PKC include –

Inhibitors

Activated PKC inhibition mechanisms of action

DGK

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