Endocrine Pancreas - Dr. Rogers Flashcards by Radhika Patel

CASE 1: 58yo m, BMI 31= Android -> midsection, (not hips and butt-> Gynoid)
rash under arm —-> Acanthosis Nigricans
Weakness, fatigue, irritable, foot ulcer not healing
Blurred vision at times
Elevated Fasting glucose and A1C
Elevated insulin and C-Peptide
Elevated BP, FAs

Metabolic Syndrome

Increased risk for = kidney, eye, liver NAFLD, vascular, heart problems, skin ulcers and wound healing

How well did you know this?

Not at all

Perfectly

Major anabolic H

Insulin and secreted in response to CHO- and protein ingestion (glucose)

How well did you know this?

Not at all

Perfectly

Endocrine Pancreas secretes

Insulin, Glucagon, Somatostatin
Lipid, carb, protein metabolism
In Islet of Langerhans
Innervation by adrenergic, cholinergic, and peptidergic neurons

How well did you know this?

Not at all

Perfectly

What does B cells secrete

Insulin and C peptide

Destroyed in Type 1 diabetes

How well did you know this?

Not at all

Perfectly

What does alpha cell secrete

Glucagon in the periphery of the islet of langerhans

How well did you know this?

Not at all

Perfectly

What does g cells and F cells secrete

Somatostatin (looks like a neuron)

PP cells, pancreatic peptide, satiety signal = neuropeptide Y)

How well did you know this?

Not at all

Perfectly

How are cells in the pancreas communicate

Tight junctions and depolarization
Blood supply comes into the middle of the islet so B cells get the most - release insulin, and later the insulin goes to the periphery of a cells to inhibit glucagon release

How well did you know this?

Not at all

Perfectly

Steps to make insulin

2 chains peptide H. (Preproinsulin) = signal peptide A + B and C Peptide
Proinsulin= C peptide and insulin in granules
Insulin and C peptide

How well did you know this?

Not at all

Perfectly

Insulin Resistance person

What is role of insulin

Type 2
Insulin tells adipose and muscle to take up glucose and store it
Insulin tells liver to stop making free glucose

This person has very high insulin and high glucose in blood

How well did you know this?

Not at all

Perfectly

How is insulin released

Glucose enters B-cell by GLUT2
Glucokinase phosphorylates glucose
G-6-P is oxidized = ATP made
ATP closes K+ channels (prevent K+ to leak out= depolarization)
voltage CA+2 channels open (Ca+2 enter cell)
AP, insulin and C peptide inside viscose are released

How well did you know this?

Not at all

Perfectly

What does Sulfonylurea receptors drugs do

Bind to the ATP-dependent K+ channel

Keeps K+ channel closed longer, to keep cell depolarized longer for Type 2 diabetics to release more insulin

How well did you know this?

Not at all

Perfectly

For is Insulin Released on a graph

It is biphasic so there is a quick initial peak followed by a slow rise for 30-60min
Type 2 : no first peak

How well did you know this?

Not at all

Perfectly

Insulin resistance happens first where

In the periphery, liver, muscle, fat

How well did you know this?

Not at all

Perfectly

How does insulin cause glucose uptake

Insulin binds to insulin receptor
Phosphorylates, P13K,Akt,mTOR, MAP kinase
GLUT 4 transporter is moved to plasma membrane of the cell
GLUT 4 brings glucose into the cell (facilitated diffusion)

How well did you know this?

Not at all

Perfectly

What happens in the cell during insulin resistance

MITOCHONRIAL OVERLOADING
Inhibits these chemical reactions to happen when insulin binds
= GLUT 4 does not move to the plasma membrane

How well did you know this?

Not at all

Perfectly

What stimulates insulin release

Glucose, ACh, CCK
Glucagon (just to modulate not too much glucose released), GIP, GLP-1
Cortisol, K, Vagal stimulation 
Sulfonylurea drugs
Obesity

What inhibits the relates of insulin

Somatostatin, Exercise, NE, Hypoglycemia drugs

Incretin Effect

HEALTHY: eat sugar and high increases in insulin

TYPE 2 progressively: eat sugar, GI does not absorb all and not a lot of insulin is released

Insulin effect on K

Increased uptake into cells

Exercise caused increased glucagon why

Becuz glucose is taken up without insulin = AMP-Kinase activated and causes GLUT 4 to move to plasma membrane
and that causes glucagon to be released to increase blood glucose
= Blood glucose stays about the same except in long distance

Glucagon and glucose coming to the a-cell

The glucose comes to the a-cell
The cascade causes inhibition of Ca+2 voltage gated channels
This makes no depolarization or AP and no glucagon is released

Glucose——> g cell and causes somatostatin release

What stimulates glucagon

ACh, high AA (alanine and arginine)

CCK, adrenerguc agents, Fasting

What inhibits glucagon release

Somatostatin, FAs, Ketoacids

Who is in risk of getting TYPE 2 diabetes

40% likely if one parent is
70% if both parents are
African Americans, Native Americans (10X higher), Hispanics

Environmental cues that increase risk of type 2 diabetes

Excess calories, Sedentary behavior Rapid postnatal growth Sleep deprivation Chronic inflammation - adipose tissue recruits macrophages, that causes inflammation of the adipose and tell them to release cytokines (IL-6, TNF-a, IFN-g, CRP) + releases FAs + disrupts lepton and adipokines Maternal disease- while baby is in the uterus

Progression of Insulin Resistance

1. Systemic resistance to insulin 2. Reactive hyperinsulinemia = after meal you have high insulin, however normal blood glucose 3. After eating you have high glucose , only fasting glucose is normal 4. INCRETIN RELEASE 5. Chronic elevated insulin 6. Chronic elevated glucose =Hyperglycemia (5-30 years to go through all this)

What happens first high insulin or high glucose in the progression of type 2 diabetes

High elevated insulin

TX for T2D

Weight reduction, caloric restriction, PE(lower insulin) Metformin- Biguanide drugs = make you more sensitive to insulin Insulin Secretagogoues = makes you release more insulin Slow CHO- absorption Bariatric Surgery *CONSTANT MONITORING IS REQUIRED of A1C

T1D

B-cells destroyed by T-cells autoimmune = no insulin and no C-peptide Sx: when 80% of b-cells are destroyed Increased ketoacids, blood glucose

Diabetic Ketoacidosis (DKA)

When you don’t uses ketoacids anymore

T1D and K

Hyperkalemia, high K outside the cell Low insulin = low Na/K pump Plasma levels of K can be low due to increased thirst

Diabetes and increased urine and thirst

Increased Glucose in the blood = water drawn into the kidney tubules and excreted No reabsorption of water and electrolytes

Development of T1D

Family history 30% if mom needs dad both has it 3-6% if one has it (higher if dad)

Which gene is mutated in the T1D

``` DQ2/DQ8 or DR3/DR4 Of HLA class 2 lack of Asp57 Most have other autoimmune problems ```

Some environmental risk factors of developing autoimmune disorders that can cause T1D

``` Early exposure to cow milk, not breast feeding VIT D deficiency Wheat gluten (Celiac Disease) only few childhood infections Obesity Viral infections of mumps, rubella.... ```

When to take insulin for T1D

Depends on when you eat (you want to take before meal) and you need to consider if you exercised and if you’re going to exercise and other factors (cortisol)

T1D Sx:

Ketosis (not is T2D) Even more intensely elevated glucose No insulin no C-peptide More likely to have hyperkalemia

Incretin effect

Food in GI causes Hs to be released that tell B-cells to release insulin, this is dysfunctional

Initial spike of insulin in normal people causes

Prevents initial spike in glucose after eating