THE ENDOCRINE PANCREAS
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108 Terms
What are the 2 functions of the pancreas?
Exocrine for digestion
Endocrine for blood glucose regulation
What does the exocrine pancreas produce?
Pancreatic juice containing:
Digestive Enzymes
Electrolytes
Water
What does pancreatic juice digest?
Carbohydrates, proteins, and fats
What regulates the exocrine pancreas?
GI hormones, pancreatic hormones, and the ANS
What are the main islet cells of the endocrine pancreas?
β (beta), α (alpha), δ (delta), and F cells
Where are β cells located in the islets?
Mainly in the center
What percentage of islet cells are β cells?
About 60%
What hormone do β cells produce?
Insulin
Where are α cells located in the islets?
Mainly in the periphery
What percentage of islet cells are α cells?
About 30%
What hormone do α cells produce?
Glucagon
Where are δ cells located?
Scattered throughout the islets
What hormone do δ cells produce?
Somatostatin
Where are F cells located?
Scattered throughout the islets
What hormone do F cells produce?
Pancreatic polypeptide
What is the source and main function of insulin?
Produced by β cells
What is the source and main function of glucagon?
Produced by α cells
How does glucagon raise blood glucose?
By stimulating glycogenolysis and gluconeogenesis
What is the function of somatostatin?
It inhibits insulin and glucagon
What is the function of pancreatic polypeptide?
Regulates appetite and acts on the hypothalamic satiety center
What other hormones raise blood glucose?
Growth Hormone
Catecholamines
Glucocorticoids
What do these other glucose-raising hormones increase?
Glycogenolysis and gluconeogenesis
What is the normal blood glucose range in non-ruminants?
About 50–175 mg/dL
What factors affect blood glucose in adult ruminants?
Age and GI development
Where does fermentation occur in ruminants?
Rumen, reticulum, and omasum
Which volatile fatty acid is glucogenic?
Propionate
Which volatile fatty acids are ketogenic?
Acetate and butyrate
Why do adult ruminants absorb very little dietary glucose?
Because microbes use carbohydrates before they reach the small intestine
What causes diabetes mellitus?
↓ Insulin production or insulin resistance
What is the main result of diabetes mellitus?
Hyperglycemia
Why do cells become energy deficient in diabetes despite high blood glucose?
Without effective insulin, glucose uptake and amino acid uptake decrease
What happens to glucose uptake without insulin?
↓ Glucose uptake
What happens to amino acid uptake without insulin?
↓ Amino acid uptake
Why does hyperglycemia cause glycosuria?
Blood glucose exceeds the kidney's reabsorption capacity
What is the sequence of effects caused by severe hyperglycemia?
Glycosuria → osmotic diuresis → water loss → electrolyte loss → polyuria → polydipsia
What is glycosuria?
The presence of glucose in urine
What is osmotic diuresis in diabetes?
Excess glucose in the urine draws water into the urine, increasing urine production
What are the major clinical effects of diabetes mellitus?
Poor metabolism of carbohydrates, fats, and proteins, metabolic acidosis, coma, and potentially death without insulin
What are the cardinal signs of diabetes?
3 Ps + glycosuria: polyphagia, polyuria, polydipsia, and glycosuria
What are the 3 Ps of diabetes?
Polyphagia, polyuria, and polydipsia
What is the basic structure of insulin?
A polypeptide of about 6,000 Da containing an A (α) chain and B (β) chain
What connects the A and B chains of insulin?
2 disulfide bonds
What stimulates insulin synthesis/release?
↑ Blood glucose
Where is preproinsulin synthesized?
In the RER
How many amino acids does preproinsulin contain?
110 amino acids
What happens to preproinsulin?
Its signal peptide is removed, forming proinsulin
What happens to proinsulin?
The C-peptide is removed, producing insulin
Where does insulin processing occur before storage?
In the Golgi
What are the products of proinsulin cleavage?
Insulin + C-peptide
In what ratio are insulin and C-peptide released?
1:1
How is recombinant human insulin produced?
Using genetically engineered E. coli
What are advantages of recombinant human insulin?
It causes less antibody formation and is preferred over bovine or porcine insulin
How is insulin released from pancreatic granules?
Granules move to the cell membrane, fuse with it, and release insulin + C-peptide by exocytosis
Where does newly released insulin enter first?
The portal circulation
What second messengers can glucose stimulate in β cells?
cAMP, IP₃, and DAG
What do cAMP, IP₃, and DAG activate?
PKA and PKC
What is the result of activating these signaling pathways?
Insulin secretion
What is the ATP mechanism of insulin secretion?
↑ Glucose → ↑ ATP → closes ATP-sensitive K⁺ channels → membrane depolarization → opens voltage-gated Ca²⁺ channels → ↑ intracellular Ca²⁺ → insulin exocytosis
What happens to ATP when blood glucose increases in β cells?
ATP increases
What happens to ATP-sensitive K⁺ channels when ATP increases?
They close
What happens to the β-cell membrane when K⁺ channels close?
The membrane depolarizes
What channels open after β-cell depolarization?
Voltage-gated Ca²⁺ channels
What triggers insulin exocytosis?
↑ Intracellular Ca²⁺
What increases insulin release through calcium?
Hypercalcemia and calcium administration
What decreases insulin release through calcium?
Hypocalcemia and calcium channel blockers
What is the main stimulus for insulin release?
Glucose
Which nutrients stimulate insulin secretion?
Glucose
Amino Acids
Fatty Acids
Which GI hormones stimulate insulin secretion?
Secretin, CCK, gastrin, and GIP
Which hormones stimulate insulin secretion?
Growth hormone, cortisol, estrogen, and progesterone
Which part of the ANS stimulates insulin secretion?
The parasympathetic nervous system
Which drugs stimulate insulin secretion?
Sulfonylureas, tolbutamide, and glibenclamide
Which hormones inhibit insulin secretion?
Somatostatin, epinephrine, and norepinephrine
Which part of the ANS inhibits insulin secretion?
The sympathetic nervous system
Which drugs inhibit insulin secretion?
Diazoxide and phenytoin
What are the major carbohydrate effects of insulin?
↑ Glucose uptake/use, ↑ glycogenesis, ↑ glycolysis, and ↓ glycogenolysis + gluconeogenesis
What is the overall effect of insulin on blood glucose?
↓ Blood glucose
What are the major lipid effects of insulin?
↑ Fatty acid and triglyceride synthesis, ↑ fat storage, ↓ lipolysis, and ↓ ketogenesis
What are the major protein effects of insulin?
↑ Amino acid uptake, ↑ protein synthesis, and ↓ proteolysis
What electrolytes does insulin move into cells?
K⁺, phosphate, and Mg²⁺
What is the structure of the insulin receptor?
It has 2 α-subunits and 2 β-subunits
Where are the α-subunits of the insulin receptor located?
Outside the cell
Where are the β-subunits of the insulin receptor located?
They cross the cell membrane and contain tyrosine kinase
What happens after insulin binds its receptor?
Tyrosine kinase activation → receptor autophosphorylation → protein phosphorylation → intracellular signaling
What are the major results of insulin receptor activation?
↑ Glucose transport, ↑ glycogen synthesis, ↑ protein/lipid synthesis, and gene regulation
What is GLUT4?
An insulin-dependent glucose transporter
Where is GLUT4 found?
Skeletal muscle, cardiac muscle, and adipose tissue
What does insulin do to GLUT4?
It moves GLUT4 to the cell membrane, increasing glucose entry
Which tissues are insulin-independent for glucose uptake?
Brain, liver, kidney, and RBCs
What are the overall effects of insulin?
↓ Blood glucose, energy storage, cell growth, and anabolism
What is the main role of glucagon?
To raise blood glucose, especially during fasting, starvation, and exercise
What stimulates glucagon release?
Hypoglycemia, amino acids, exercise, and catecholamines
What inhibits glucagon release?
Hyperglycemia, insulin, somatostatin, and free fatty acids
What are the major effects of glucagon?
↑ Glycogenolysis, ↑ gluconeogenesis, ↑ lipolysis, and ↑ ketogenesis
What is the overall effect of glucagon on blood glucose?
↑ Blood glucose
What is the source of somatostatin in the pancreas?
δ cells
What are the functions of pancreatic somatostatin?
↓ Insulin, ↓ glucagon, ↓ GI motility, and ↓ GI secretions
What is the source of pancreatic polypeptide?
F cells
What are the functions of pancreatic polypeptide?
Regulates food intake, acts on the satiety center, and helps regulate nutrient levels
What is hyperinsulinism?
Having too much insulin
What does hyperinsulinism cause?
Hypoglycemia