Pancreatic Hormones Flashcards
Insulin & Glucagon are synthesized as large ________.
preprohormones
Connecting (C) peptide
- aka disulfide bridges
- connects the 2 peptide chains of insulin
- in the case of the beta cells, inuslin & connecting (C) peptide are released into the circulating blood in equimolar amounts
- can be measured with a radioimmunoassay & is a measure of beta cell function in diabetic patients treated with insulin.
In the case of the beta cells, _______ & ________ ________ are released into the circulating blood in ________ amounts.
insulin, connecting (C) peptide, equimolar.
Insulin is a polypeptide…
containing 2 amino acid chains (21 & 30 a.a) connected by disulfide bridges.
- polypeptide chains = A & B
GLucagon is a…
straight-chain polypeptide of 29 amino acid residues.
Insulin & glucagon circulate…
unbound to carrier proteins
Insulin & glucagon - short half-lives of…
5 - 10 mins
Insulin has actions on carbohydrate, fat, & protein metabolism that occurs within seconds, minutes & hours.
A. Rapid = increased:
- glucose,
- amino acid,
- & potassium uptake into cells.
B. Intermediate
- stimulation of protein synthesis
- inhibition of protein degradation
- activation & inactivation of enzymes
C. Delayed
- increased transcription
The insulin receptor is a ______ made up of ___ ____ subunits that lie outside the cell membrane & ___ ______ subunits that penetrate the cell membrane & protrude into the cytoplasm.
tetramer, 2 alpha, 2 beta.
Metabolic effect of Insulin
The binding of insulin to the alpha subunit of the receptor triggers tyrosine kinase activity of the beta subunits, producing autophosphorylation of the beta subunits on tyrosine residues.
This results in the phosphorylation of other intracellular proteins & enzymes, which mediates a multitude of responses.
Glucose transporters
A large family of structurally related transport proteins
2 main types of Glucose Transporters
- Sodium-glucose linked transporters (SGLTs)
- Facilitated diffusion glucose transporters (GLUTs)
Transporters differ in terms of…
their substrate specificity, distribution & regulatory mechanisms.
The primary regulatory mechanism by which glucose uptake takes place is…
via insulin-stimulated transport of glucose into skeletal muscle & adipose tissue, primarily mediated by glucose transporter protein type-4 (GLUT4)
CLASS 1 =
GLUT 1 - 4
CLASS 2 =
GLUT 5 - 11
CLASS 3 =
GLUT 6 - 13
The function of glucose sensing has 2 components:
- Entry of glucose into the cell mediated by GLUTs
- Metabolism of glucose through phosphorylation by glucokinase
GLUT 1
- expressed mainly on human beta cells
- in hepatocytes, GLUT1 is associated with the bidirectional transport of glucose controlled by hormones such as thyroid hormone.
GLUT 2
- expressed mainly in beta cells of the pancreas, liver & kidney.
- acts as a glucose sensor in the beta cells of marine organisms.
In vitro animal & clinical studies have shown that…
the primary pancreatic beta cell sensor is glucokinase & not GLUT1 or GLUT2.
GLUT 3
- mainly present in the brain
- has a high infinity for glucose, a property which is consistent with its function to transfer glucose into cells having a higher requirement of glucose.
GLUT 4
- is an insulin-responsive glucose transporter that is found in the heart, skeletal muscle, adipose tissue, & brain. (Primarily in skeletal muscle & adipose tissue)
- present in the cytoplasm of cells in vesicles from which it is translocated to the plasma membrane under the influence of insulin.
Insulin
- plasma half-life
- clearance from the circulation
Plasma 1/2 life = approx. 5 - 10mins
Clearance = within 10 - 15mins
