Glucose Transport and Regulation

Insulin

A peptide hormone produced by the beta cells of the pancreas that promotes glucose uptake from the blood into skeletal muscle and adipose (fat) tissue, lowering blood glucose.

Beta cells

Pancreatic cells that produce and release insulin.

Effect of insulin on blood glucose

Decreases blood glucose by promoting glucose uptake into cells, especially skeletal muscle and adipose tissue.

Glucagon

A peptide hormone produced by the alpha cells of the pancreas that increases blood glucose by stimulating the liver to release glucose into the bloodstream.

Alpha cells

Pancreatic cells that produce and release glucagon.

Effect of glucagon on blood glucose

Increases blood glucose by stimulating the liver to break down glycogen and produce glucose.

Glycogenolysis

The breakdown of glycogen into glucose so glucose can be released into the bloodstream.

Gluconeogenesis

The production of glucose from non-carbohydrate sources, such as amino acids and glycerol.

Glucocorticoids

A type of steroid hormone that increases and maintains blood glucose concentrations, partly by stimulating gluconeogenesis in the liver.

Effect of stress on glucocorticoids

Stress can increase glucocorticoid levels, which can contribute to increased blood glucose.

Insulin signaling

The process through which insulin binds to its receptor on a cell and signals the cell to increase glucose uptake.

Insulin receptor

A receptor on the cell membrane that binds insulin and begins the signaling pathway that promotes glucose uptake.

GLUT4

A glucose transporter that moves to the cell plasma membrane in response to insulin, allowing glucose to enter skeletal muscle and adipose cells.

GLUT4 translocation

The movement of GLUT4 transporters to the cell membrane in response to insulin so that glucose can enter the cell.

Insulin → GLUT4 pathway

Insulin binds to its receptor → activates intracellular signaling → GLUT4 moves to the cell membrane → glucose enters the cell → blood glucose decreases.

Figure F14: Insulin interaction with insulin receptors

Insulin binds to insulin receptors and causes GLUT4 to translocate to the cell plasma membrane, allowing glucose to enter the cell.

Insulin resistance

A condition in which cells do not respond normally to insulin, resulting in reduced glucose uptake and impaired blood glucose regulation.

Insulin resistance in T2DM

Cells have impaired insulin signaling, so glucose uptake is reduced and blood glucose remains elevated.

Insulin receptor changes in T2DM

Type 2 diabetes can involve decreased insulin receptor binding affinity and/or fewer functional receptors, reducing the effectiveness of insulin signaling.

Inflammation and insulin signaling

Inflammation can interfere with normal insulin signaling and contribute to insulin resistance.

Impaired insulin signaling in diabetes

Diabetes can involve weakened signaling pathways that reduce the cell's ability to respond to insulin and transport glucose into the cell.

AS160 phosphorylation

A signaling step involved in insulin-stimulated glucose transport; weakened AS160 phosphorylation in skeletal muscle can impair glucose uptake.

PKC λ/ζ activity

Activity of protein kinase C isoforms involved in insulin signaling; impaired PKC λ/ζ activity can contribute to impaired glucose transport.

HF/HC diet

A high-fat/high-carbohydrate diet that can affect insulin sensitivity and glucose regulation.

Insulin sensitivity

How effectively cells respond to insulin and take up glucose from the blood.

Decreased insulin sensitivity

Cells require more insulin to produce the same response, making it more difficult to move glucose from the blood into cells.

Metabolic pathway regulation

The body controls metabolic pathways by changing enzyme activity in response to hormones and cellular energy status.

Hormonal induction or activation of enzymes

Hormones such as insulin, glucagon, and glucocorticoids can activate or induce specific enzymes involved in metabolism.

Insulin and metabolic pathways

Insulin generally promotes pathways that use or store glucose, such as glycolysis and glycogenesis.

Glucagon and metabolic pathways

Glucagon generally promotes pathways that increase available blood glucose, such as glycogenolysis and gluconeogenesis.

Glucocorticoids and metabolic pathways

Glucocorticoids help maintain blood glucose, including by stimulating gluconeogenesis in the liver.

Allosteric enzyme regulation

Enzyme activity can be increased or decreased when molecules bind to regulatory sites on enzymes.

ATP

A molecule that reflects cellular energy availability and can regulate metabolic enzymes through allosteric effects.

ADP

A molecule associated with lower cellular energy availability that can influence metabolic enzyme activity.

NAD

A coenzyme involved in oxidation-reduction reactions that also helps regulate metabolic pathways based on the cell's metabolic state.

Positive modulation

Regulation that increases enzyme activity.

Negative modulation

Regulation that decreases enzyme activity.

Glycogenesis

The synthesis/storage of glycogen from glucose.

Glycogenolysis

The breakdown of glycogen to release glucose.

Glycolysis

The breakdown of glucose to produce energy and metabolic intermediates.

Hexose monophosphate shunt

Another name for the pentose phosphate pathway, which metabolizes glucose-6-phosphate and produces NADPH and pentose sugars.

Citric acid cycle

Also called the Krebs cycle or TCA cycle; an aerobic metabolic pathway that oxidizes acetyl-CoA and produces energy-related molecules.

Gluconeogenesis

The production of glucose from non-carbohydrate sources, especially during periods when blood glucose needs to be maintained.