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physiology-of-endocri-doc

By Leslie Simpson,2014-08-02 11:31
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physiology-of-endocri-doc

    Physiology of Endocrine Pancreas

    I. Anatomy

    a. Islets of Langerhans

    i. β cells

    1. 65% - insulin

    ii. α cells

    1. 20% - glucagon

    iii. Delta cells

    1. 10% somatostatin iv. Remaining

    1. Pancreatic polypeptide

    b. Communications

    i. Gap Junctions

    1. α ? β

    2. etc

    ii. blood supply

    1. venous supply of one bathes the others

    iii. α cells “neural”

    1. adrenergic

    2. cholinergic

    3. peptidergic receptors

    4. onto β cells

    II. Insulin

    a. Struture and Synthesis i. Peptide hormone

    1. A chain

    2. B chain

    3. 3 disulfide bridges ii. Chromosome 11

    iii. Preproinsulin

    1. A + B chains + C-peptide

    2. clipped to PROInsuLIN will being made as PREPRO

    iv. Packaged in Golgi

    1. cleaved to insulin + C-Peptide

    2. SECRETED TOGETHER

    3. C-peptide levels measured in urine of IDDM to test β

    cell function

    b. Factors affecting Insulin

    i. (+)

    1. ? glucose

    2. ? AA

    3. Glucagon

    4. GH

    5. Cortisol

    6. Gastric inhibitory peptide (GIP)

    7. Potassium

    8. Vagal stim (ACh)

    9. Sulfonylurea drugs

    a. tolbutamide

    b. glyburide

    10. Obesity

    ii. (-)

    1. ? glucose / fasting

    2. Exercise

    3. SS

    4. α agonists

    5. diazoxide

    c. Mechanism of Secretion

    i. Xport of glucose into β cell

    1. GLUT2 transporter pro

    2. facilitated diffusion ii. Metx of glu inside β cells

    1. glu is Phosphorylated iii. ATP closes K+ channels

    1. ? ATP ? ? K+ channels

    a. Depolarizes cell

    iv. Depolarization opens voltage gated Ca2+ channels

    v. ? intracellular Ca2+ causes insulin secretion

    1. pancreatic venous blood ? systemic

    2. insulin + C-peptide released EQUIMOLAR

    3. Oral glu > IV glu @ ? insulin

    a. d/t oral ? GIP

    i. independent (+) on insulin

    4. Glucagon

    a. ? intracellular Ca2+ ? ? insulin

    5. SS

    a. Inihibits mechanism of glucagon

    b. ? insulin

    6. sulfonylurea drugs (NIDDM)

    a. tolbutamide

    b. glyburide

    c. close ATP-dependant K+ channels

    i. depolarized cells (mimics insulin)

    d. Mechanism of Action

    i. Insulin receptor

    1. 2x α subunits

    2. 2x β subunits

    3. tyr-kinase

    ii. Steps

    1. Insulin binds to α subunit

    a. Activates tyr-kinase in β subunit

    b. Autophosphorylation

    2. activated tyr-kinase

    a. activates other pro

    3. insulin-receptor complex is internalized (endocytosis)

    a. insulin DOWN REGULATES itself

    i. ? synthesis

    ii. ? degradation

    iii. SEEN IN OBESITY AND NIDDM

    4. Insulin (+) gene transcription of somatomedians

    e. Actions of Insulin

    i. ? blood glucose

    1. ? glu oxidation

    2. ? GNG

    3. How? (away from glu formation)

    a. ? glu transport into cells (GLUT4)

    b. ? glycogenesis

    c. ? GNG

    i. ? fructose 2,6 bisphosphate

    ii. ? PFK

    ii. ? FFA and ketoacid concentrations

    1. ? lipogenesis

    2. ? lipolysis

    iii. ? AA concentration

    1. ANABOLIC

    iv. Other actions

    1. ? K+ uptake into cells

    a. ? Na-K ATPase

    2. (+) hypothalamic SATIETY CENTER

    f. Pathophysio

    i. Type I (IDDM)

    1. destruction of β cells ? NO INSULIN made

    a. measure c-peptide in urine

    b. autoimmune

    2. Presents

    a. ? [glu]

    b. ? [FFA] and ? [ketoacid]

    i. Metabolic acidosis

    ii. Diabetic ketoacidosis (DKA)

    c. Polyuria + Polydipsia

    i. Too much glu in collecting duct

    ii. Cannot filter

    iii. In urine as OSMOTIC DIURETIC

    d. Hyperkalemia

    i. No activation of Na-K pump

    ii. K+ stays outside ii. Type II NIDDM

    1. obesity

    2. MOA

    a. DOWN REGULATION OF RECEPTORS

    b. “insulin resistance”

    3. Presents

    a. ? [glu]

    i. Fasting and post-meal

    4. Tx

    a. Fastic + wgt loss

    b. Sulfonylurea drugs

    i. Tolbutamide

    ii. Glyburide

    iii. (+) insulin secretion

    c. Biguanide drugs

    i. Metformin

    ii. UPREGULATES Recptors

    III. Glucagon

    a. Structure and Synthesis

    i. Prepro ? etc

    ii. Inihibits by insulin + glucose

    b. Regulation of Secretion

    i. ? [glu]

    1. remember, insulin ultimately ? [glu] w/c causes ?

    glucagon secretion

    2. esp scene in NIDDM

    a. no (-)FL of insulin ii. Factors Affection Secretion

    1. (+)

    a. Fasting ?[glu]

    b. ? AA (esp l-arg and l-ala)

    c. Cholecystokinin (CCK)

    i. (+)

    1. pro or fat ingestion

    2. fasting and exercise

    d. Β agonists

    e. ACh

    2. (-)

    a. Insulin

    b. SS

    c. ? FFA and ketoacid

    iii. Actions

    1. adenylyl cyclase via cAMP

    2. Liver only

    a. Insulin: liver, SkM, adipose

    3. ? [glu]

    a. ? Glycogenolysis

    b. ? GNG

    4. ? FFA and ketoacid

    a. Ketoacids

    i. Acetoacetate

    ii. Β-hydrobutric acid

    IV. Somatostatin (SS)

    a. Delta cells

    b. Differenence between pancreatic v. GI SS

    i. 14 v 28 AA

    c. Releasing factors

    i. (+)

    1. ingestion of all nutrients

    2. glucagon

    3. β agonists

    ii. (-) insulin (paracrine)

    d. Actions

    i. ? secretion of insulin and glucagon

    ii. Fctn

    1. modify/limit the action of I/G upon ingestion

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