Endocrine PHYSIOLOGY

*KEY POINT: C-peptide is marker of Endogenous Insulin synthesis.(insulin and C-peptide are released together from secretory granules)*So with EXOgenous insulin it will be decreased as ENDOgenous synthesis will be suppressed .vs*With insulinoma and Sulfonylurea use ENDOgenous insulin synthesis and secretion is INCREASED.*if you suspect insulinoma, for screening you can need abdominal CT.

*Proinsulin is cleaved into INSULIN and Inactive C-peptide inside the SECRETORY GRANULES.*Well then insulin leaves the cell by EXOcytosis(Those secretory granules travel towards the plasma membrane and help insulin leave the cell)

IMage is illlegal draw it.*Well, you should know structure of PROinsulin(alpha,Beta chains,DISULFIDE Bonds and C-peptide) then if you know that insulin doesn't have C-peptide attached to it you can deduce that anything that is different from Proinsulin but has C-peptide is PREPROinsulin and then anything that looks like proinsulin but has no C-peptide should be insulin.*SUPER HY: PREPRO INSULIN is Synthesized in ROUGH endoplasmic Reticulum.

*GLUT 2 transporter is bidirectional transporter which is located on B islet cells of PANCREAS(Cells which actually SECRETE Insulin), but other HY locations include SMALL intestine,LIVER,KIDNEY.*This bidrectional transporter is Insulin INdependent and is probably most HY insulin independent transporter(know locations too).

*First of them non of them is insulin dependent.*Glucose is transported by GLUT2 while GLUT 5 transports FRUCTOSE(Just remember FivE for FructosE)

*FRUCTOSE(Not glucose) and trough GLUT5.

*So you should know that GIP and GLP-1 are Incretins(Hormones secreted by ENTEROendocrine cells)

**GLUT1 and GLUT3 are both Insulin-INdependent and are present in BRAIN and PLACENTA.*Other hy locations for GLUT 1 you should know for step 1 : RBCs,CORNEA.you should know that GLUT1 and GLUT3 are HIGH-affinity(Low Km) and HIGH Capacity(High Vm) transporters.

*GLUT-2.

*GLUT 4 is INSULIN dependent and is located on ADIPOCTES/SKELETAL Muscle(Often tested), also if they ask mechanism by which exercise can help diabetic patient,the answer will be increased expression of GLUT 4.*NOW now this daigram(DRAW IT -ILLEGAL)Note how GLUT 2 has Higher Vm(Rate)-capacity and HIGHER Km(LOWER affinity for glucose), GLUT 4 has Lower Vm(Lower capacity) and Lower Km(Higher affinity).....recall from biochem very similar relationship between Hexokinase(Tissues except liver and pancreas) and Glucokinase(Liver,B-islets),remember Hexokinase has Low Km(High affinity) but low Vm(low capacity) so hexokinase is like GLUT 4 while Glucokinase has High Km(Low affinity) and High Vm(High capacity) and thus resembles GLUT2.

*It binds TYROSINE KINASE receptors(HY)>2 subunits AUTOPHOSPHORYLATE each other,eventually increasing activity of PHOSPHOINOSITIDE-3 KINASE pathway(Leading to increased Protein,Lipid,Glycogen synthesis and synthesis/transport of GLUT4 which is how glucose will enter those cells) insulin also stimulates RAS/MAP kinase pathway which increases cell growth and promotes DNA synthesis.

*DECREASES it by causing increased reabsorption>Na Retention.

*Trough glycolysis Intracellular glucose increases ATP levels in the cells(Thus increased ATP/ADP ratio), thus increased ATP levels CLOSE ATP-sensitive K channels(This Closure is promoted by SULFONYLUREAS)>K can't Exit the cells>Cell becomes DEPOLARIZED and Voltage-gated Calcium channels OPEN>Increased INTRAcellular calcium>EXOcystosis of secretory granules packed with insulin.

*GLUCOSE only.they will tell you that mother injected insulin and will ask MECHANISM of decrease in glucose levels of FETUS, the answer will be decrease in mother's blood glucose levels(less glucose is left for baby)=INdirect effect, it seems easy in flashcard form but bunch of sophisticated distractor answer choices could mess u up.

*Alpha 2 activation DECREASES insulin release vs B2 activation INCREASES insulin release.this is often tested.*WELL Normally INSULIN is ANABOLIC(Promotes building not degradation), so it DECREASES lipolysis.So we would expect that alpha 2 activation which leads to DECREASED insulin release would result in Increased lipolysis BUT alpha 2 activation results in DECREASED LIPOLYSIS(So if in answer choices for alpha 2 receptor activation you see Decreased lipolysis and Decreased insulin release do NOT get confused)vsB2 activation leads to INCREASED Insulin release but also increased lipolysis(again contrary to what insulin does which would normally Decrease lipolysis)just remember that alpha2 decreases insulin release and beta2 increases insulin release then just remember that lipolysis will follow the same direction(with alpha 2 it is decreased vs with B2 it is increased)...This is the case when overthinking will make you loose point.