Endocrine Pancreas Flashcards by Morgan Mcbride

Where are B cells located and what do they secrete?

centrally in the islet
Secrete insulin and C peptide

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Where are alpha cells and what do they secrete?

Peripherally located
Secretes glucagon

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Where are delta cells and what do they release?

Interspersed btw alpha and beta cells
Secrete somatostatin
neuronal appearance sending dendrite like processes to beta cells

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What are F cells and secreteion?

Secretes pancreatic polypeptide
Acts like a satiety singal similar to NPY

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How do cells within the islets communicate?

Ion concentration changes signals via gap junctions

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What is the blood supply to the islets?

10% of pancreatic blood flow and venous blood from B cell carries insulin to alpha and delta cells
- blood flow first to center for insulin and flows through the periphery on alpha cells inhibiting glucagon releases

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What are the precursors tto insulin?

Preproinsulin, proinsulin, and insulin and C peptide
Preproinsulin is a signal peptide with A and B chains with connectring C peptide
Proinsulin lacks a signaling peptide and still has C peptide attached, packed into secretory granules and proteases cleave proinsulin
C peptide is used as a marker of endogenous insulin secretion

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Steps to insulin release?

Glucose enters the cell via GLUT2
Glucose is phosphorylated by glucokinase
G6P is oxidized promoting ATP generation
ATP closes inward rectifying K channel
Plasma mem is depolarized
Activation of voltage gated CA channels
Ca enters cell and initiates mobilization of insulin & C peptide vesicles to plasma membrane and exocytosis occurs

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With insulin release, rises in ATP ___ the K channels.

Closes

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What do Sulfonylurea receptors do?

They are associated with the ATP dependent K channels and they increase insulin secretion causing memnrane depolarization to occur easier allowing more Ca entry. They are used for T2DM treatement

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What are the intracelllular steps to insulin signaling?

insulin binds receptor
Substrate proteins phosphoorylate and activate/inactivate downstream paths
1. MAP kinases and Akt major ones
Translocation of vesicles containing GLUT 4 to membrane of mm and adipose and glucose enters via facilitated diffusion

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With T2DM what is a hypothesis for insulin resistance?

Mitochondrial overload and lack of GLUT4 moving to membrane to take in glucose

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What initiates release of insulin?

GI peptides,glucagon, somatostatin, ACh

CCk ACh use PLC
Glucagon and GIP use GPCR Gs to stimulate

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What is the role of somatostatin with insulin release?

Somatostatin uses GPCR Gi to inhibit

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What happens to the incretin effect with T2DM?

Incretin effect to tell beta cells to release insulin is reduced in T2DM

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What are inhibitory factors for insulin secretion?

Ecercise
fasting
somatostatin
alpha adrenergic agonists
Diazoxide
Decreased blood glucose

Insulins actions on skeletal mm?

increase glu uptake
increase glycogen syn
increased glycolysis and CHO oxidation
Increase protein syn
Decrease protein breakdown

Insulin actions on liver?

Promotes glycogen syn
increase glycolysis and CHO oxidation
decrease gluconeogenesis
increase hexose monophosphate shunt
increase pyruvate oxidation
increase lipid store and decreases oxidation
increase protein synthesis decrease breakdown

insulin on adipose?

Increase glu uptake

increased glycolysis

decrease lipolysis

promote uptake of fatty acids

What is the effect of insulin with K?

It promotes K uptake into cells therefore decreasing blood levels of K

How does exercise effect blood sugar and insulin?

Muscle contraction stimulates glucose uptake via GLUT4
Blood sugar usually stays close to normal
Insulin may decrease
Eating too close to exercise can dirupt the glucose homeostasis

What is the metabolic role of Glucagon?

glucagon increases blood glucose
increases gluconeogenesis
increases lipolysis
increases glycogenolysis
inhibits glycogen syn

Stimulates insulin secretion

What stimulates release of glucagon?

Increased amino acids specifically alanine and arginine
Fasting
CCK
Beta adrenergic agonists
ACh
Stimulated by decreased blood glucose

What inhibits glucagon?

Insulin and high blood glucose levels

also somatostatin, fatty acids and ketoacids

What factors contribute to T2DM?

* Multiple genes coupled with environement * African Americans, hispanics and native americans are at a higher risk * Children with one parent are at 40% risk and those with two parents are at 70% risk

What are environmental exposures that contribute to T2DM?

* excessive caloric intake * sedentary behavior * maternal disease and nutrition * rapid postnatal growth * sleep debt * chronic inflammation

How does adipose tissue dysfunction and chronic systemic inflammation contribute to T2DM?

* Inflammed adipiose tissue recruits M1 macrophages and releases more inflammatory markers disrupting adipokines and releasing fatty acids * IL-6 and other cytokines such as TNFa IFNy and CRP

Describe the progression of insulin resistance?

1. Systemic insulin resistance 2. Reactivve hyperunsulinemia 3. Postprandial hyperglhycemia 4. Disrupted response to oral glucose tolerance test 5. Blunted incretin release 6. Chornic elevated insulin 7. Milkd to moderate chronically elevated glucose levels 8. Hyperglycemia

Compare T1DM and T2DM?

Type 1: * peaks in childhood * ketosis is common at onset * family history 10-20% * Autoimmune pathophys and other assoc. autoimmune disorders * Overtly elevataed blood glucose * Absent insulin and C peptide Type 2: * Post pubertal onset and uncommon ketosis at onset * \>50% family history * Insulin resistance pathophys * OBesity lipid abnormalities PCOS NAFLD associated * Mild to moderate elevation of blood glucose * Insulin and C peptide elevated until later in progressioni

What are some treatments for T2DM?

Lifestyle changes: * caloric restriction,weight reduction,physical activity/exercise Drugs/surgeries: * Biguanide drugs such as metformin and TZDs * Insulin secretagogues: sulfonylurea drugs and incretin analog of GLP-1 * a-glucosidase inhibitors and amylin analogs * Bariatric surgery

What is T1DM, when do symptoms present?

* An autoimmune disorder where T cells destroy the Beta cells resulting in no insulin or C peptide. * symptoms aren't seen until 80% of Beta cells are destroyed * Patients will have an increased blood glucose, fatty acids, ketoacids, amino acids, increased conversion of fatty acids to ketoacids * Decreased utilization of ketoacids results in DKA

Describe the hyperkalemia seen in type one diabetics?

* intracellular concentration of K is low * the lack of insulin effects the Na/K ATPase * Plamsa levels of K can be normal, but the total K is usually low due to polyruria and dehydration