Energy regulation of the pancrease

The cell types in the Islets of Langerhans and what they secrete

alpha cells secrete    glucacon    that ^ BS

beta cells secrete    insulin       that v BS

delta cells  secrete somatostatin

these are NOT regulated by the pituitary or hypothalmus

regulated mainly by glood glucose

-----lesser effect from amino acids

regulated by negative feedback

**glucose enters the brain by facilitated diffusion**

normal fasting BS is 65 - 105 mg / dl.

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High blood glucose (increases)  = then glucose binds to GLUT 2  receptor protein in beta cells

stimulating production and release of insulin

glucose binds to GLUT 2 when blood sugar rises

and insulin stimulates skeletal muscle cells and adipocytes to incorporate

GLUT 4 (glucose facilated diffusion carrier)

into the plasma membrane

insulin promotes anabolism

 insulin stimulates skeletal muscle cells and adipocytes to incorporate

GLUT 4 (glucose facilated diffusion carrier)

into the plasma membrane

insulin promotes anabolism

intestinal hormones stimulate insulin activity

insulin is released when you eat

All three hormones GIP, GLP-1, and CCK stimulate insulin in anticipation of increased blood glucose

Effects of autonomic nerves

on insulin and glucagon secretion

Parasympathetic nervous system (calm)

stimulates insulin secretion

Sympathetic nervous system (excited)

stimulates glucagon secretion

Insulin is the major hormone that promotes anabolism in the body ***

When blood insulin increases these things happen:

promotes cellular uptake of glucose

(facilitative diffusion)

1. Stimulates glycogen storage in the liver and muscles

2. Stimulates triglyceride storage in adipose cells (lypogenesis)

3. Promotes cellular uptake of amino acids and synthesis of protein

Glucogen between meals by glyconeogenesis

Maintains blood glucose concentrations

When blood glucagon*** is increased:

1. stimulates glycogenolysis (ONLY IN THE LIVER) 

in the liver (glucose-6-phosphatase)-- 

2. Stimulates gluconeogenelysis

3. Skeletal muscles, heart, liver and kidneys use fatty acids as a major souorce of fuel (hormone-sensitive lipase)    

 stimulates lipolysis and ketogenesis  (anabolic and catabolic responses)

Remember only  in the  liver  glycogenolysis

Effects of feeding and fasting on metabolism

feeding increases glucose which

increases insulin and decreases glucagon

the effects are

the formation of glycogen, fat, and proten

^ glycogon, fat and protein

v  blood glucose        goes down

v  blood amino acids   goes down

v   blood fatty acids    goes down

v   ketone bodies      goes down

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Fasting decreases blood glucose

decreases insulin and increases glucagon

the effects are

hydrolysis of glycogen, fat and protein

+ gluconeogensis and ketogenesis

v glycogon, fat and protein

^  blood glucose        goes up      

^  blood amino acids   goes up

^   blood fatty acids    goes up

^   ketone bodies      goes up

Measures the ability of beta cells to secrete insulin

the ability of insulin to lower blood glucose

Normal person's rise in blood glucose after drinking solution is reversed to normal in 2 hours

chronic high blood glucose

2 forms: 

1.  Type 1:        insulin dependent diabetes (IDDM)

2.  Type 2:  non-insulin dependent diabetes (NIDDM

Type 1 diabetes mellitus =

beta cells of the islets of Langerhans are destroyed by autoimmune attack which may be provoked by environmental agent

Glucose cannot enter the adipose cells with out insulin which causes the rate of fate synthesis to lag behind the rate of lypolysis...and fatty acids convert to ketone bodies producing ketoacidosis

Increased blood glucagon  that stimulates glycogenolysis in the liver

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consequences of uncorrected deficiency in type 1 diabetes mullitus:

high liver glycogenolysis  + high liver gluconeogenesis

and so low glucose use and hyperglycemia

and osmotic diuresis H20, Na, K Ca,P

dehydration, volume depletion, hypotension

PUPD  =  drink and urinate  thirst and urinate

high liver ketogenesis    high lipolysis

decreased keton utilization

hypoketonemia

metabolic acidosis

slow to develop

Genetic actors are significant

most often occurs in overweight (even 5 or 10 lbs)

Do not respond to insulin 

Tyrosine kinase not activated

Decreased sensitivity of cells to insulin = insulin resistance---obesity=fat interfers

Do not usually develop ketoacidosis

may have high or normal insulin

PUPD  drink and urinate

lifestyle change

increase exercise + increases the amount of membrane GLUT-4 carriers in the skeletal muscles

weight reduction

increased fiber in diet

reduced saturated fat

Not Adkins diet = bad for kidneys

adrenal medulla part of sympathetic nervous sisten...

similar effects to glucagon

metabolic effects similar to glucagon

stimulates glycogenolysis

---stimulates release of glucose from liver

---stimulates lipolysis and release of fatty acids

glucocorticoids are secreted in response to

ATCH

glucocorticoids support the effects of increased glucagon

Promote lipolysis  and ketogenesis

Promote protein breakdown in the muscles  (increases blood amino acids)

Promote liver gluconeogenesis

mineral = aldosterone

glucocortical = cortison

follicular cells
active form is T3   

increase T3     decreases TSH  like in Graves Disease 

Stimulates cellular respiration by

 production of uncoupling protein

Stimulation of active transport Na+/K+ pump

(lowers ATP by using it up)

Increases metabolic heat

Increases metabolic rate

Contributes to proper growth and development of CNA in children

Lack of prenatally and 6 mo postnatally = creatinism

Aldosterone is a hormone that increases the reabsorption of sodium ions and water

and the release (secretion) of potassium ions

in the cortical collecting ducts and collecting ducts of the kidneys.

This increases blood volume and, therefore, increases blood pressure.

Aldosterone is a yellow steroid hormone

 mineralcorticoid family)

produced by the outer-section (zona glomerulosa) 

of the adrenal cortex,

and acts on the the kidney to cause the conservation of Na+, secretion of K+, increased water retention, and increased BP.

The overall effect

of aldosterone

is to increase reabsorption

of ions and water in the kidney.

aldosterone is reduced in Addison disease

increased in Conn syndrome

Growth Hormone

Somatotropin

hypothalmus GhHR

Inhibited by somatostatin

stimulates growth in kids and adolescents

Stimulated by GHRH

causes increase in blood amino acids

decrease in blood glucose

pulsatile, increasing during sleep, decreasing during day

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inhibited by IGF 1

IGF 1 is produced in the liver in response to GH...it stimulates cell division and growth of cartilage

IGF 2 has more insulin-like actions

liver produces and secretes IFG-1 in response to GH

It  stimulates  cell division  and growth of  cartilage

More insulin - like actions

promotes anabolism          and catabolism

reduction                hydrolysis

stimulates cellular uptake of amino acids and protein synthesis

Raises blood glucose

Growth Hormone and effects on body growth

gigantism = excess secetion in children

maintain normal body proportions

Acormegaly

Excess GH secretion in adults after  epithyseal discs are sealed

no increase in height

Growth of soft tissue

elongation of jaw, deformities in hands, feet and bones of face

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Dwarfism = inadequate

¾³Bone deposition and reabsorption

CA++ and phosphate concentrations are affected by:

bone formation and resorption

Intestinal absorption of Ca++  and PO4---

Urinary excretion

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Osteoblasts secrete and organic matrix of collagen proteins

Deposit hydroxyapatite crystals

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Osteoclasts secrete enzymes to dissolve hydroxyapatite

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Formation and resorption of bone occur constantly at rates determined by osteoblasts and osteoclasts

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Bone resorption occurs when and osteoclast attaches to the bond matrix and forms ruffled membrane

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Osteoclast secretes products that dissolve both Ca++ and PO4³-:  and digest the matix

----Transport of H+ aby H+ ATPase pump in ruffled border

----Cl- channel allows Cl- to flow to H+ to maintain electrical neutrality

___________________________

Protein matrix digested by cathepsin K releasted by osteoclasts

THE single most important hormone in control of Ca++

---stimulated by decreased blood Ca++

Stimulates osteoclasts to reabsorb bone

Stimulates kidneys to reabsorb Ca++ from glomerular filtrate, and inhibit reabsorption of PO4³-

Promotes formation of 1, 25 vitamine D3

Works with PTH and 1, 25 vitamin D3 to regulate blood Ca++

Stimulated by increase of plasma Ca++

Inhibited by activity of osteoclasts

Stimulates urinary excretion of Ca++ and PO4³- by inhibiting reabsorption

Physiological significants in adults is questionable

1, 25 Vitamin D3 (1, 25-Dihydroxyvitamine D3)

Pre-vitamine D3 is synthesized in the skin when exposed to mid-ultrviolet waves

---previtamin D3 isomerized to vitamine D3 (cholecalciferol)

Cholecalciferol is hydroxylated in the liver to form 25-hydroxycholecalciferol

In proximal convoluted tubules is hydroxylated to

1, 25- dihydroxycholecalcifer (active vitamin D3)

---Stimulated by PTH

Directly stimulates intestinal absorption of ca++ and PO4³-

When Ca++ intake in inadequate ,  directly stimulates bone reabsorption

Stimulates reabsorption of Ca++ and PO4³- by the kidneys

---simutaneously raising Ca++ and PO4³- results in increased tnedency of these 2 ions to precipitate as hydroxyapatite crystals

Stimulated by PTH