Regulation of Metabolism Flashcards
What does insulin do in general?
initiates events that promote removal of glucose, also fatty acids and amino acids from blood thus preventing hyperglycemia.
Glucagon Catecholamines Glucocorticoids Growth Hormone Hormones of the Gut
All regulate biochemical processes which help to elevate the plasma glucose levels to prevent hypoglycemia.
What is the quaternary structure of insulin?
• Insulin consists of 2 peptide chains held together by S-S bridges, MW 6000. The whole molecule is needed for activity.
Where is insulin synthesized?
What are the stages of preliminary to active hormone?
- Synthesis occurs in β cells (B cells) of Islets of Langerhans.
- pre-proinsulin
- proinsulin
- insulin and C-peptide.
What are the Products secreted by β cells of the Islets of Langerhans?
- Insulin
- C-peptide (in approximately equal amounts with insulin)
- proinsulin.
Does proinsulin have activity?
• Proinsulin has 50% of the immunoreactivity of insulin and 5% of its biological activity.
What is the primary control of Insulin release?
Primary stimulus: high blood glucose level (this also stimulates insulin synthesis).
What are modulating factors of insulin release?
• certain amino acids (especially arginine) • ketones • glucagon • gut peptide hormones • catecholamines • prostaglandins • somatostatin • CNS. Mechanism involves a glucose sensor (glucokinase), glucose metabolism and coupling of glucose metabolism via the ATP/ADP ratio leading to ionic events governing insulin secretion. The key factor for insulin secretion is the calcium ion concentration.
What is the half-life of Insulin?
What is the half-life of Proinsulin?
What degrades insulin?
What degrades proinsulin?
Inuslin: Half-life ~ 10 min; degraded primarily by hepatic proteolytic enzymes.
Proinsulin: half-life is 20 min; degraded by kidney enzymes.
Review: Mechanism of Action of Insulin:
Insulin binds to a cell surface receptor (a transmembrane protein). In the presence of its ligand the receptor can function as a tyrosine kinase. This leads to autophosphorylation of the receptor and phosphorylation of key docking proteins (IRS and Shc). This results in the activation of a series of parallel downstream events that involve a cascade of covalent phosphorylation reactions and protein-protein interactions, which ultimately results in modulation of specific cell functions including glucose transport, glycogen and protein synthesis and mitogenesis.
Review: Mechanism of Action of Insulin:
Insulin binds to a cell surface receptor (a transmembrane protein). In the presence of its ligand the receptor can function as a tyrosine kinase. This leads to autophosphorylation of the receptor and phosphorylation of key docking proteins (IRS and Shc). This results in the activation of a series of parallel downstream events that involve a cascade of covalent phosphorylation reactions and protein-protein interactions, which ultimately results in modulation of specific cell functions including glucose transport, glycogen and protein synthesis and mitogenesis.
What is Insulin actions on muscle?
- Stimulation of glucose transport into the cell.
- Enhancement of glycogen synthesis.
- Stimulation of amino acid uptake.
- Stimulation of protein synthesis.
- Inhibition of proteolysis.
NB: Exercise also stimulates glucose transport into muscle cells.
What is Insulin actions in adipose tissue?
- Stimulation of glucose uptake into the cells.
- Promotion of fat synthesis.
- Activation of lipoprotein lipase.
- Inhibition of hormone-sensitive lipase.
- Enhancement of glycogen synthesis.
- Enhancement of amino acid uptake and protein synthesis
What is Insulin actions on liver?
- Stimulation of glucokinase and glycogen synthetase activity.
- Stimulation of activities of key rate limiting glycolytic enzymes (phosphofructokinase, pyruvate kinase and pyruvate dehydrogenase).
- Inhibition of activities of the key rate limiting gluconeogenic enzymes (glucose-6-phosphatase, fructose-1,6-diphosphate phosphatase, phosphoenolypyruvate carboxykinase and pyruvate carboxylase).
- Stimulation of fatty acid synthesis and increase in activities of key lipogenic enzyme.
Where is Glucagon degraded?
Does it reach peripheral tissues?
Where is proglucagon degraded?
Distribution and degradation — Degraded very rapidly in liver and thus it is questionable whether any glucagon normally reaches peripheral circulation. Proglucagon, however, is degraded in kidney and its biological activity is minimal.
What tissues have glucagon receptors?
Glucagon receptors — Cell surface receptors have been identified in liver, fat, myocardial cells and pancreatic islet β-cells.
