Pancreas Physiology L25 | Physiology 2 Exam 3

What are the four hormones secreted by islets of langerhans in pancreas

• beta cells: insulin

• alpha cells: glucagon

• D cells: somatostatin

In insulin synthesis, what are the three stages of insulin products ( including the final stage of insulin synthesis)

1. preproinsulin

2. proinsulin

3. insulin

How insulin formed in Beta cells of islets of langerhans using N-terminus and C-terminus within the cells’ sequence

1. signal sequence is removed from preproinsulin creating → proinsulin

2. Chain C is removed from proinsulin → creating insulin

What chains and sequences are present in insulin

only chain A and chain B

In beta cells, if signal sequence is removed from preproinsulin, what should form

proinsulin

In beta cells, what needs to be removed to form insulin

• signal sequence (from preproinsulin)

• Chain C (from proinsulin)

What is the purpose of insulin secreted by beta cells w regards to cell regulation of glucose

inc enhancement cells to use glucose = dec blood glucose

What stimulates beta cells in islet of lagerhans to begin glucose regulation/dec BG

inc in BG, hyperglycemia, causing glucose to funnel into beta cells via GLUT2

What is amylin (in regards to pancreas)

amylin (islet amyloid polypeptide or IAPP):

• inhibits food

• delays gastric emptying

• dec BG

• dec BW

What is C-peptide (in regards to pancreas)

Commonly used indicator for B-cell function (C-peptide: Commonly used indicator)

After elevated BG and glucose transports into beta cells of pancreas, what occurs to glucose

inc respiration that promotes ATP production from glucose

As ATP production increases in beta cells from glucose entering the cell, what two channels are affected causing what ion-reaction

1. closes K-ATP channel causing depolarization (bc of inc K in cell)

2. Depolarization leads to voltage-gated Ca channels to open increasing Ca inside the beta cell

As BG elevates and glucose enters beta cells in pancreas, Ca channels open activating [what] that promotes exocytosis

insulin gene expression via CREB (calcium responsive element binding protein) promoting exocytosis

After BG increases and CREB promotes exocytosis, what are the products that are exocytozyed in the blood

• insulin (overall dec glucose)

• C-peptide (common indicator of B-cell function)

• Amylin (inhibits food intake and dec BG)

Where are GLUTs transporters found compared to SGLTs transporters (related to pancreas physiology)

GLUT: ubiquitous (all cells express)

SGLT:

1. intestine

2. renal tubules; kidneys

3. BBB

Comparing GLUTs and SGLTs transporters, which are sodium dependent vs independent

GLUT: sodium and ATP-independent

SGLT: sodium-dependent

Out of all the GLUT and SGLT transporters, which one is insulin-dependent and where is it located in the body

GLUT-4 - insulin-dependent

• skeletal muscle

• adipose tissue

• heart

Comparing SGLT 1 vs SGLT 2, how do they interact with glucose and where are they found

SGLT1: glucose absorption; found in enterocytes of intestine

SGLT2: glucose retention; found in proximal tubules of kidneys

What is the main anabolic function of insulin (from beta cells of pancreas) in regards to storage

BY STORING GLUCOSE IN TISSUE:

• causes dec BG

• dec FA

• dec AA

What is the function of insulin in liver

to enhance glycogenesis OR glycolysis

END RESULT: inc ATP or glycogen

How does insulin affect the liver to promote glycogenesis or glycolysis (the entire pathway of insulin in liver)

1. insulin (in blood) binds to tyrosine-kinase receptor (in liver)

2. binding to tyrosine-kinase receptor activates PI3K/AKT

3. activation causing two reactions (in liver)

   1. glycogenesis

      1. GLUT-2, insulin independent transporter, transports glucose into liver

      2. PI3K/AKT promotes glycogenesis

      3. creating glycogen

   2. glycolysis

      1. GLUT-2, insulin independent transporter, transports glucose into liver

      2. PI3K/AKT promotes glycolysis

      3. creating pyruvate turned into Acetyl-CoA into krebs cycle for ATP production

Why does insulin not enhance glucose uptake in PI3/AKT activation in liver

GLUT-2 is insulin independent

What is the function of insulin in skeletal muscles

to enhance:

• glucose uptake

• glycogenesis

• glycolysis

• amino acid uptake

• protein synthesis

What is the function of insulin in skeletal muscles in regards to glucose

to enhance:

• glucose uptake

• glycogenesis

• glycolysis

What is the function of insulin in skeletal muscles in regards to amino acids/proteins

to enhance:

• amino acid uptake

• protein synthesis

How does insulin affect the muscles to promote glycogenesis or glycolysis (the entire pathway of insulin in muscle regarding glucose)

1. insulin (in blood) binds to tyrosine-kinase receptor (in muscles)

2. binding to tyrosine-kinase receptor activates PI3K/AKT

3. activation causing three reactions involving glucose (in muscle)

   1. glucose uptake

      1. via PI3K/AKT activates GLUT-4 enhance glucose uptake into muscle cells

   2. glycogenesis

      1. GLUT-4, insulin dependent transporter via PI3-AKT, transports glucose into muscle

      2. PI3K/AKT promotes glycogenesis

      3. creating glycogen

   3. glycolysis

      1. GLUT-4, insulin dependent transporter via PI3-AKT, transports glucose into muscle

      2. PI3K/AKT promotes glycolysis

      3. creating pyruvate turned into Acetyl-CoA into krebs cycle for ATP production

How does insulin affect the muscles to promote protein synthesis (the entire pathway of insulin in muscle regarding amino acids)

1. insulin (in blood) binds to tyrosine-kinase receptor (in muscles)

2. binding to tyrosine-kinase receptor activates PI3K/AKT

3. activation causing two reactions involving amino acids (in muscle)

   1. AA uptake

      1. via PI3K/AKT activates AA channel enhance AA uptake into muscle cells

   2. protein synthesis

      1. AA channel, insulin dependent transporter via PI3-AKT, transports AA into muscle

      2. PI3-AKT promotes protein synthesis creating proteins

What is the function of insulin in adipose tissues

to enhance:

• glucose uptake

• lipogenesis

How does insulin affect adipose tissues to promote lipogenesis (the entire pathway of insulin in adipose tissue regarding glucose and lipogenesis)

1. insulin (in blood) binds to tyrosine-kinase receptor (in adipose tissue)

2. binding to tyrosine-kinase receptor activates PI3K/AKT

3. activation causing two reactions involving glucose (in adipose tissue)

   1. glucose uptake

      1. via PI3K/AKT activates GLUT-4 enhance glucose uptake into adipose tissue

   2. lipogenesis

      1. GLUT-4, insulin dependent transporter via PI3-AKT, transports glucose into adipose tissue

         • in adipose tissue, some glucose becomes converted through glycolysis into Acetyl-CoA (and finally ATP)

      2. PI3K/AKT promotes conversion of glucose to glycerol

      3. PI3K/AKT promotes conversion of Acetyl-CoA to FFA via lipogenesis

      4. Glycerol + FFA = triaclyglycerol

Which diabetes mellitus is most common in dogs

Type 1 diabetes

Which diabetes mellitus is most common in cats

Type 2 diabetes

What is the cause for diabetes meallitus

high BG levels

Which type of diabetes mellitus is insulin resistant

Type 2 diabetes mellitus

What are the differences of cause of type 1 vs type 2 diabetes mellitus

type 1: caused by destruction of beta cells by immune cells leading to insulin insufficiency

type 2: inability of cells to respond to insulin

What is the cause of type 1 diabetes mellitus

type 1: caused by destruction of beta cells by immune T cells leading to insulin insufficiency

What is the cause of type 2 diabetes mellitus

type 2: inability of cells to respond to insulin

Which type of diabetes mellitus is insulin responsive

type 1 diabetes mellitus

With insulin insufficiency from type 1 diabetes, what tissues are affected and their response/clinical symptoms

• adipose tissue → lipolysis: fat breaks down

• skeletal muscle → protein breaks down

→ weight loss + hunger = polyphagia

With insulin insufficiency from type 1 diabetes, what organ is affected and their response/clinical symptoms

kidney secretes glycosuria → inc urine osmolality and polyuria (urination) → polydipsia (dehydrated; drinks a lot)

What is the tx for type 1&2 diabetes and the tissues affected

(lifelong) insulin therapy provides tx to:

• adipose

• muscle

In the pathogenesis of diabetic ketoacidosis, how does formation of ketone bodies from liver occur

1. adipose tissue release fat that is converted into FA with lipolysis

2. Liver uses FA to create Ketone-bodies (aceotoacetic, Beta-hydroxybut

In the pathogenesis of diabetic ketoacidosis, what ketone bodies are formed from fatty acids produced by adipose tissues

• acetoacetic acid

• beta-hydroxybutyric acid

In the pathogenesis of diabetic ketoacidosis, the ketone bodies (acetoacetic acid & beta-hydroxybutyric acid) forms what that causes fruity breath

acetone

In the pathogenesis of diabetic ketoacidosis, the ketone bodies (acetoacetic acid & beta-hydroxybutyric acid) forms what that causes ketoacidosis

• inc acidity of blood

  • ketoacidosis

• energy

In the pathogenesis of diabetic ketoacidosis, the ketone bodies (acetoacetic acid & beta-hydroxybutyric acid) forms what products

1. energy

2. inc acidity of blood (= ketoacidosis)

3. acetone (= fruity breath)

What three clinical signs are formed from ketoacidosis

1. kussmual respiration - deep, rapid labored breathing

2. high anion gap

3. hyperkalemia

In ketoacidosis, what is the result of kussmaul respiration

(deep, rapid labored breathing to try to detox blood)

1. reduce CO2

2. reducing acidity

In ketoacidosis, what is the cause of hyperkalemia, a complication of Type 1 diabetes

1. inc H+ into cells

2. K+ leaves the cell

3. Insulin insufficiency due to Type ! diabetes leading to malfunction of Na/K pump

   1. no K+ into cell

4. leading to hyperkalemia

What is the cause of kussmaul respiration and hyperkalemia from ketoacidosis’ effect

inc acidity in blood = H+ inc

What is the cause of high anion gap from ketoacidosis, a complication of Type 1 diabetes

1. buildup of ketoacids

2. large differences in unmeasured ions

   → high anion gap

What is the normal range of anion gap (related to ketoacidosis

3-11MEQ/L

How are anion gaps forms from partial anion calculation

anions that are not accounted for when cations and anions are calculated

True of false: ketoacidosis can not occur during insulin therapy

false

What are three ways to reduce ketoacidosis

1. fluids for dehydration

2. insulin to lower BG

3. electrolytes (K+)

During Type 2 diabetes mellitus, what causes beta-pancreatic cell hyperplasia/hypertrophy

due to compensation of insulin resistance → Beta cells work harder to try to lower glucose

What are the effects of long-term Beta-pancreatic cell hyperplasia/hypertrophy from type 2 diabetes

hypoplasia/hypotrophy

True or False: Diabetic Ketoacidosis is not common in Type 2 diabetes

True

What is the most commonly associated disease with type 2 diabetes

hyperosmolar hypergylemic state (HHS)

In type 2 diabetes with increased blood glucose levels, how does hyperosmolar hyperglycemic state cause dehydration in the cell

inc glucose in the blood inc plasma osmolality causing dehydration of cells

What is the result of dehydration of the cells from hyperosmolar hyperglycemic state

inc urination (glucouria)

sometime mild ketonemia and acidosis

What is the result of inc urination due to dehydration of the cells from hyperosmolar hyperglycemic state

total body dehydration → mental status changes

What are the four tx for type 2 diabetes

1. weight loss

2. exercise

3. healthy diet

4. antidiabetic meds

How does antidiabetic meds treat type 2 diabetes

inhibits hepatic glyconeogenesis → normoglycemia

What are complications due to uncontrolled Type I, II diabetes mellitus in vessels

• hyaline artheriolosclerosis

• capillary BM thickness

• atherosclerosis in medium/large arterial walls

In uncontrolled Type I, II diabetes mellitus in vessels, how do arterioles develop hyaline arteriolosclerosis

• hyaline deposits

  • which become hard and inflexiable

In uncontrolled Type I, II diabetes mellitus in vessels, how do capillary BM leads to more acidosis

BM becomes thickened leading to hypoxia = more acids produced

In uncontrolled Type I, II diabetes mellitus in vessels, what is the result of large/medium arterial wall damage

atherosclerosis → heart attack/stroke

What are the three tissues that are affected by uncontrolled Type I, II diabetes mellitus

• eyes

• kidneys

• nerves

In uncontrolled Type I, II diabetes mellitus of the eyes, what clinical signs do you see

diabetic retinopathy → blindess

• cotton wood spots

• flare hemorrhage

In uncontrolled Type I, II diabetes mellitus what occurs to the kidneys

damaged glomerulus leading to nephrotic syndrome

In uncontrolled Type I, II diabetes mellitus, what occurs to nerves leading to amputation

autonomic nervous system dysfunction leading to:

• poor blood supply

• nerve damage

  → causing ulcers (leading to amputation)

what are the four different dx tests we can use to test for BG levels

1. fasting glucose - no food or drink for 8 hours

2. non-fasting/random glucose - anytime

3. oral glucose - give glucose and measure at intervals

4. HbA1c - proportion of Hb w glucose attached to it

What test measures byproduct of insulin (and what would the result be in pancreas experiencing diabetes I)

C-peptide (byproduct of insulin) measures insulin levels; low or absent in pancreas experiencing diabetes I

What test can only be performed for Type I diabetes (and why)

C-peptide bc measures byproduct of insulin (and insulin would not be present in type I diabetes that has insulin insufficiency)

Where is glucagon metabolized

• liver

• kidney

What are the four stimuli for glucagon release

• hypoglycemia

• autonomic nervous system

• protein ingestion (release both insulin and glucagon)

• intestinal hormones (release both insulin and glucagon)

How does hypoglycemia cause an increase glucagon secretion

1. dec glucagon creates a detrend of ATP in the Alpha cell

2. W/ lower ATP, closes K channels

3. inc K+, inc positive ions = depolarizing membrane potential

4. Voltage-gated Ca channels that attach to glucagon in alpha cell

5. alpha cell exocytosis to inc glucagon

Through