endocrine - pancreas Flashcards
Secreted in equinolar amts as insulin.
Measured in the blood to quantify endogenous insulin production
C-peptide
Insulin is catabolic/anabolic
Anabolic
Insulin is stored in secretory granules in Zn-bound crystals. It is released by exocytosis of granule contents ff by endocytosis. It has 2 biphasic release
1st (early phase)
2nd (late phase)
Biphasic phase of insulin that is short lived and prompt.
1st (early phase )
Biphasic phase of insulin that involves release of preformed insulin.
First or early phase
Biphasic phase of insulin that is responsible to peak insulin secretion after meal
First or early phase
Biphasic phase of insulin that is slower onset and maintained for considerable periods
2nd or late phase
Biphasic phase of insulin that involves release of newly formed insulin.
2nd or late phase
Peak of first or early phase
5 min
Duration of 2nd phase
10 min - 1 hr
Half life of insulin
5-8min
Insulin is degraded by what enzyme found in liver, kidney and other tissue
Insulinase
Insulin is responsible for maintaining the upper limit of blood glucose and FFA by
Promoting glucose uptake and utilization by muscle and adipose tissue
Increase glycogen storage in liver and ms
Decrease glucose output by liver
Insulin action
Promotes protein synthesis Inhibits protein degradation Ptromotes TGL synthesis Inhibits lipolysis Has effects on satiety
Primary stimulus and regulator of insulin
Glucose
Entry kg glucose into B-cells is facilitated by
Glut-2 transporter
Glucose is phosphorylated into G6P by what enzyme
Glucokinase
Glucose sensor of B cells
Glucokinase
Regulation of insulin
Glucose enters Bcells by glut-2 Glucose to G6P by glucokinase Send signals to increase ATP/ADP ratio Closes K channel Depolarize Opens Ca channel CA entry Stimulates insulin secretory granule Release insulin thru exocytosis
Insulin mechanism of action
Insulin binds to IR
Initiates series of phosphorylation reaction and gene expression
Glut-4 transports glucose from outside to inside
Glycogen, lipid and protein synthesis
Insulin receptor has a and B subunit. Which subunit is external to cell membrane?
Alpha subunit
Insulin receptor has a and B subunit. Which subunit contains hormone binding site?
Alpha subunit
Insulin receptor has a and B subunit. Which subunit spans the cell membrane.
Beta subunit
Insulin receptor has a and B subunit. Which subunit contains tyrosine kinase on cyto solid surface?
Beta subunit
Insulin + receptor results to cross phosphorylation of B subunits leading to recruitment of adaptor proteins such as..
IRS (insulin-receptor substrates)
SHC protein
APS protein
IRS phosphorylation leads to activation of..
Protein kinase B (PKB) dependent pathway
Resulting to metabolic effects of insulin.
Termination of Insulin/IR signaling
- Insulin down- regulates own receptor by receptor-mediated endocytosis and degradation pathways
- Inactivation of IRS protein by serine/threonine protein kinase
- Activation of “suppressor cytokines signaling” SOCS which reduces acty levels of IR and IRS proteins.
Action of insulin
*Glucose uptake (by GLUT-4 availability in ms and fats)
*Glucose use
Glycogenesis
*Glycolysis
Decrease glycogenolysis
Specific in liver FA synthesis and VLDL decrease gluconeogenesis Decrease x Decrease urea cycle activity
Specific in ms
Aa uptake
Protein synthesis
Decrease proteolysis
Specific in adipose tissue
Production of a-glycerol phosphate
Esterification of fats
Decrease lipolysis
Insulin is catabolic/anabolic
Catabolic
Primary counter regulatory hormone of insulin
Glucagon
Glucagon is a primary counter regulatory hormone by
Increase bld glucose thru hepatic glucose output
Increase glucose production thru (increase glycogenolysis, gluconeogenesis, and decrease glycolysis, glycogenesis and inhibits FFA synthesis from glucose)
Glucagon circulates in bound/ unbound form
Unbound form
Thus has short half life of 6min
Primary site of degradation of glucagon
Liver
80% in single pass
Primary target organ of glucagon effect
Liver
Determines net flow of hepatic metabolic pathway
Insulin/glucagon ratio
Major stimulus of glucagon
Low blood glucose
Stimulates glucagon secretion
Low blood glucose High aa (arginine, alanine)
Sympa NS stimulation (B2 adrenergic)
Stress
Exercise
Inhibits glucagon secretion
Somatostatin
Insulin
High blog glucose
Somatostatin is also found in
Hypothalamus and GIT
Somatostatin has 2 forms
Somatostatin-14
Somatostatin-28
Importance of somatostatin is not clearly established but..
It can inhibit insulin and glucagon secretion thru paracrine mechanisms depending in what the body needs
Pancreatic polypeptide is stimulated by
Various GIT hormone
Vagal stimulation
