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Lower amounts of glucose in the blood inhibit insulin and stimulate glucagon secretion:

Leads to the breakdown of glycogen stores in order to increase blood glucose levels

The sympathetic nervous system also plays a role in the control of secretion:

Noradrenaline inhibits insulin release

Adrenaline stimulates glucagon release

Glucose enters the muscle due to acute muscle contractions stimulating GLUT4 translocation to the membrane.
Chronic exercise increases GLUT4 expression and thus the ability to take up glucose by the cells.

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Varying secretion concentrations of glucagon and insulin according to glucose amount

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Varying secretion concentrations of glucagon and insulin according to glucose amount

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Glucagon promotes the breakdown of glycogen -
By inhibiting:

Glucokinase expression

Glycogen synthase activity

By activating:

Glycogen phosphorylase

G6Pase

Glucagon promotes gluconeogensis -
By inhibiting:

Glucokinase

Phosphofructokinase activity

Pyruvate kinase

PEPCK

FBPase

-- all key enzymes in promoting the storage glucose to glycogen

Glucagon also promotes lipid oxidation.

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You have done really well!

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Insulin promotes:

Glucose uptake via GLUT4

Glycolysis to give precursors for lipogenesis

Lipogenesis is the formation of fat

Synthesis of lipoprotein lipase

Lipoprotein lipase is a water-soluble protein that hydrolyses triglycerides in lipoproteins

It is responsible for the processing and absorption of fats

Inhibits hormone-sensitive triglyceride lipase

This enzyme is responsible for mobilising stored fats

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Insulin promotes:

Glucose uptake via GLUT4

Glycogen synthesis through hexokinase expression and glycogen synthase activity

Hexokinase phosphorylates glucose to form glucose-6-phosphate

Glycogen synthase is a key enzyme is glycogen formation

Glycolysis and oxidation via phosphofructokinase activity and pyruvate dehydrogenase

Oxidation occurs when pyruvate is oxidised to CO2

Phosphofructokinase is a key enzyme in the glycolysis pathway

Pyruvate dehydrogenase is part of the pyruvate dehydrogenase complex (PDC) and contributes to transforming pyruvate to acetyl CoA

Protein synthesis

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Insulin stimulates enzymes - glucokinase, glycogen synthase activity

Glucokinase facilitates phosphorylation of glucose to glucose-6-phosphate --> leads to glycogen formation and storage of glucose

Glycogen synthase aids in this conversion and storage

Insulin also inhibits glucose-6-phosphate, glycogen phosphorylase

Glucose-6-phosphate is the transition-state between glucose and glycogen synthesis and glucose and glycolysis

Glycogen phosphorylase is a key enzyme in glycogenolysis (breakdown of glycogen stores)

Maintains a concentration gradient and promotes further entry of glucose into the hepatocyte

Insulin promotes lipid storage and protein synthesis as well as inhibits gluconeogenesis

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Stimulated by insulin binding to receptor and activating downstream pathways

Cytoplasmic vesicles containing GLUT4 undergo exocytosis positioning GLUT4 on the cell membrane

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High levels of glucose, amino acids and fatty acids in the bloodstream stimulate the insulin receptor on beta cells and insulin is released

Insulin acts as anabolic hormone on liver, skeletal muscle & adipose tissue

This increases the storage of glucose, fatty acids and amino acids

Impaired insulin secretion = diabetes mellitus

Insulin secretion is also stimulated/inhibited by the autonomic nervous system:

Parasympathetic nervous system stimulates via the vagal nerve.

At the beginning of a meal the vagal nerve stimulates the GI tract and uses a feedforward response that stimulates insulin release so that insulin is readily available when food arrives to the stomach.

Sympathetic nervous system inhibits in a fight or flight response.

It promotes breakdown of glycogen in order to provide energy for 'flight'

Gastrointestinal hormones stimulate including gastrin, secretin, gastric inhibitory peptide

Mechanism of action

Insulin binds to the tyrosine kinase receptor

This causes autophosphorylation

Activates tyrosine kinase

Phosphorylates proteins such as IRS family

Activates downstream pathways e.g. MAP kinase

Leads to activation/deactivation of enzymes and induce/suppression of gene expression

Stimulates glucose uptake by GLUT4 in skeletal muscle as well as adipose tissue and by enzymes in liver

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During fasting state (low blood glucose - hypoglycaemia) gluconeogenesis occurs which stimulates the alpha cells to produce glucagon

Stimulated by high blood amino acids and low fatty acid levels

Infection and exercise also stimulates

As does cortisol

Somatostatin inhibits

Glucagon acts as a catabolic hormone to mobilise glucose, fatty acids and amino acids from stores to blood

Impaired glucagon secretion can be compensated (no disease state)

Acts as a functional antagonist to insulin

Major site of action is the liver and adipose tissue

Glucagon secretion is also stimulated/inhibited by the autonomic nervous system:

Sympathetic nervous system stimulates via adrenaline and the beta-adrenoceptor to conserve energy.

Mechanism of Action

Glucagon receptor a GPCR predominantly found in hepatocytes

Glucagon binds to it's receptor and causes a conformational change

The G-alpha stimulatory subunit breaks away and stimulates adenylate cyclase

This forms cAMP from ATP

cAMP activates protein kinase a (PKA)

PKA phosphorylates key enzymes in gluconeogenesis

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Following a meal the blood glucose is increased -> glucose is taken up via facilitated diffusion by GLUT transporters.

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Necessary for maintaining brain function

Provides energy for cells

Persistent HYPERGLYCAEMIA - high blood glucose (>30-40 mM) leads to osmotic diuresis and signs of diabetes mellitus

HYPOGLYCAEMIA - low blood glucose (<2-3 mM) leads to confusion, seizures, coma

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Carbohydrates

Glucose <--> Glycogen

Lipids

Fatty acids <--> Triacylglyceride

Proteins

Amino acids <--> Proteins

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The most important energy source for all cells.

Only form of energy for brain - essential for normal CNS function