Hormonal Regulation of Blood Glucose and Metabolism

Insulin

Lowers blood glucose by promoting uptake and storage.

Glucagon

Raises blood glucose by stimulating glycogen breakdown and gluconeogenesis.

β-islet cells

Secrete insulin.

α-islet cells

Secrete glucagon.

Gluconeogenesis

Not performed by muscle cells due to lack of glucagon receptors and glucose-6-phosphatase.

GLUT4

Responsible for insulin-stimulated glucose uptake in muscle and fat cells.

Insulin signaling

Activates PI3K, facilitating RAB/RALA GTPase activation for GLUT4 vesicle transport and fusion.

mTORC1 activation

Activated by growth factors, high ATP:AMP ratio, and amino acids (arginine, leucine, SAM).

Activated mTORC1

Promotes protein and RNA synthesis, stimulates glycolysis, and inhibits autophagy.

Essential GTPases for mTORC1

RagA (nutrients) and Rheb (ATP levels).

mTORC1 localization

Localized at the lysosome membrane for activation.

mTORC1 in cancer therapy

Target because it's often upregulated in cancers and contributes to unchecked growth.

SCAP

Protein that senses cholesterol levels in the ER and binds SREBP.

Low cholesterol levels

SCAP-SREBP moves to Golgi, SREBP is cleaved, and the transcription factor domain enters the nucleus to increase cholesterol synthesis.

HMG-CoA reductase

Rate-limiting step in cholesterol synthesis.

HMG-CoA reductase regulation

Regulated by feedback inhibition by cholesterol via sterol-sensing and proteolysis.

HIF-1α

Transcription factor that responds to low oxygen.

Genes activated by HIF-1α

EPO, glycolytic enzymes, VEGF, PDGF.

HIF-1α under high oxygen

Ubiquitinated and degraded.

Heat shock response trigger

Accumulation of unfolded proteins due to stress or elevated temperature.

HSF1

Master regulator of the heat shock response in humans.

HSF1 regulation under normal conditions

Bound and inactivated by HSP70-ATP complexes.