the endocrine pancreas chapter 15. slide 2 exocrine : secretion of enzymes for food digestion...
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The Endocrine Pancreas
Chapter 15
Slide 2
EXOCRINE : secretion of enzymes for food digestionENDOCRINE: secretion of hormone for energy metabolism and fuel homeostasis in the body
Fx of whole pancreas: related to the overall process of digestion, uptake and use of metabolic fuel
Pancreas
Slide 3
Microscopic Anatomy of the Endocrine Pancreas
The endocrine pancreas consists of cells known as islets of Langerhans.
Pancreas contains 1 million islets.
They compose 1-2% of total mass of total mass of pancreas.
Slide 4Fig 15-3, pg 455Capillaries
Alpha Cell (rim)
Beta Cell (center)
Delta Cell
Microscopic Anatomy of the Endocrine Pancreas
Islets of Langerhans are numerous, small endocrine cell clusters having a rich blood supply.
Cell types: alpha = glucagon beta = insulin delta = somatostatin
60% 25%
Slide 5
Fig 15-4, pg 456
S
S
S
S
SS
NH2
COOH
B-chain
A-chain
NH2
COOH
Insulin has A and B chains linked by disulfide bonds.
Insulin
Slide 6
Proinsulin C-peptide excision release of A-B (insulin) plus C-peptide.
C-peptide: index of insulin production
Insulin
Slide 7
Insulin-containing vesicles release insulin by exocytosis; blood insulin is mostly free.
Insulin
Slide 8Fig 15-5, pg 457
Glucose
Insulin
Hours
Pla
sma
insu
lin (
ng
/ml)
Pla
sma
glu
cose
(m
g/1
00 m
l)
Blood insulin levels rise 10-30 fold soon after blood glucose exceeds 100 mg/dl.
Stimulus for Insulin secretion
Glucose very rapid and large increase in insulin secretion
Slide 9Fig 15-6, pg 457
Blood glucose
Insulin secretion
Plasma insulin
Glucose uptake into tissue
Blood glucose
Restoration of blood glucose to normal
Blood insulin is part of a feedback loop to maintain a constant blood glucose level.
Slide 10
Amino and fatty acids mildly stimulate insulin release.
GI hormone (gastrin/secretin) stimulate insulin release; anticipatory signal
Parasympathetic stimulates insulin release; sympathetic or epinephrine inhibits.
Glucagon and sulfonylureas stimulate release; somatostatin inhibits.
Other factor that control insulin secretion
Slide 11
Glucagon
Synthesis by alpha cells: proglucagon glucagon
Slide 12
Glucagon secretion is highest at fasting; an opposite release pattern from insulin.
Stimulus for glucagon secretion
Slide 13
Amino acids stimulate glucagon and insulin release; blood glucose level are maintained after protein-rich meal.
Fatty acids inhibit glucagon.
Effect of insulin: Glucose inhibits glucagon secretion, but glucagon stays high if insulin is absent (diabetes).
Other factor that control glucagon secretion
Slide 14
Action of insulin and glucagon
Two primary hormones involved in regulating fuel homeostasis in the body.
With two hormones, blood glucose level is maintained within narrow limits.
What for?: CNS relies almost solely on glucose for its metabolic needs.vs. high level of blood glucose loss of water
Slide 15
Insulin: hormone of nutrient abundance
When influx of nutrient is high, insulin directs storage of fuels, suppressing mobilization of preexisting fuel stores.
Slide 16
Insulin membrane receptor has tyrosine kinase activity; targets are muscle, fat, and liver.
Insulin lowers blood glucose level very rapidly and effectively.
Slide 17Fig 15-7, pg 461
Glucose
Liver
Muscle and
adipose
Blood
Plasma membrane
Glucose
Glycolysis
Cytoplasm
Citric acid cycle
Glycogen synthesis
Glycogen
Gluconeogen-esis liver)
Except for brain and liver, tissues require insulin for facilitated diffusion glucose uptake.
Insulin stimulates glycogen synthesis in liver and muscle, and glycolysis in most cells.
In liver, insulin inhibits gluconeogenesis.
Slide 18
Fig 15-8, pg 461
Glucose Glucose
Blood
Lipoproteins
LPLipase Adipose cell
Glycerol
Fatty acids
Fatty acid synthesis
AcetylCoA
-Glycerol-phosphate
Triacylglycerols
Hormone sensitive
lipase
Stimulates glucose uptake, lipogenesis, and lipid uptake in adipose; inhibits lipolysis.
Lipid metabolisum
Liver
Stimulates uptake of lipoprotein
Slide 19Fig 15-9, pg 462
Amino acids
Blood
Amino acids
Protein synthesis
Protein
Muscle
Protein degradation
Stimulates amino acid uptake and protein synthesis in muscle; inhibits proteolysis.
In DM, net loss of protein.
Insulin: protein metabolism 40% of total body protein is in muscle
Slide 20
Fig 15-10, pg 463
Blood
Glucose Glucose
Liver Citric acid cycle
Glycogen
Glycogenolysis
Gluconeogenesis
Glucagon has opposite cellular effects from insulin; works via cAMP; liver is main target.
Glucagon increases blood glucose.
1.
2.
3. Glucose sparing
Slide 21
Fig 15-11, pg 463
Glucose Glucose Liver
Triacylglycerols-Glycerol-phosphate
Acetyl-CoA
Fatty acids Glycerol
Hormone-sensitive lipase
Ketogenesis
Blood
Fatty acids
Ketone bodies
Ketone bodies
Glucagon stimulates liver lipolysis and ketogenesis; heart and muscle use ketones.
Glucose sparinglipolysis
Slide 22Fig 15-12, pg 464
Protein
Protein synthesis
Liver
Amino acids
Gluconeogenesis
Glucose
Ammonia
Amino acids
Urea synthesis
Blood
Urea
Protein degradation
Glucagon stimulates liver proteolysis, gluconeogenesis, and urea cycle.
Slide 23
High protein, low carbohydrate meal
Both insulin and glucagon
insulin: synthesis of protein while glucagon: maintain blood glucose level
Concerted Effects
Slide 24
Concerted Effects
High I/G (as high as 30) produces anabolism; low I/G (as low as 0.5) produces catabolism.
Ex) if insulin secretion is deficient
High blood glucose
Without insulin, glucagon secretion is not inhibited.
I/G ration; high
extremely high blood glucose
Slide 25
Concerted Effects
Most body energy stores are fats; fats have high caloric density and hold no water.
Slide 26(c) 2003 Brooks/Cole - Thomson Learning
Fig 15-13, pg 466
Liver
Muscle
Adipose tissue
BloodLPL
Fattyacids
Protein
Aminoacids
Insulin highGlucagon low
Protein
Aminoacids
Glucose
Glycogen
Protein
Amino acids
Glycogen
Glucose
Glucose
Aminoacids
Fattyacids
Lipoproteins
Fattyacids
Triacylglycerols
Glucose
-Glycerol-phosphate
-Glycerol-phosphate
Triacylglycerols
Insulin stimulates: 1) storage of ingested carbohydrates as glycogen (liver) and fats (adipose)
Slide 27(c) 2003 Brooks/Cole - Thomson Learning
Fig 15-13, pg 466
Liver
Muscle
Adipose tissue
BloodLPL
Fattyacids
Protein
Aminoacids
Insulin highGlucagon low
Protein
Aminoacids
Glucose
Glycogen
Protein
Amino acids
Glycogen
Glucose
Glucose
Aminoacids
Fattyacids
Lipoproteins
Fattyacids
Triacylglycerols
Glucose
-Glycerol-phosphate
-Glycerol-phosphate
Triacylglycerols
Insulin stimulates: 2) conversion of ingested amino acids to protein
Slide 28(c) 2003 Brooks/Cole - Thomson Learning
Fig 15-13, pg 466
Liver
Muscle
Adipose tissue
BloodLPL
Fattyacids
Protein
Aminoacids
Insulin highGlucagon low
Protein
Aminoacids
Glucose
Glycogen
Protein
Amino acids
Glycogen
Glucose
Glucose
Aminoacids
Fattyacids
Lipoproteins
Fattyacids
Triacylglycerols
Glucose
-Glycerol-phosphate
-Glycerol-phosphate
Triacylglycerols
Insulin stimulates: 3) conversion of ingested fatty acids to fats
Slide 29(c) 2003 Brooks/Cole - Thomson Learning Fig 15-14, pg 467
Liver
Muscle
Adipose tissue
Blood
Fattyacids
Insulin lowGlucagon high
Protein
Aminoacids
GlycogenGlycogen
Glucose
Glucose
Aminoacids
Fattyacids
Glycerol
Triglycerides
LP
Ketones
Ketogenesis Gluconeogenesis
Ketones
Urea
Energy
Glucose-6-phosphate
Low I/G stimulates:
1) liver and muscle glycogen and muscle protein to glucose
Slide 30(c) 2003 Brooks/Cole - Thomson Learning Fig 15-14, pg 467
Liver
Muscle
Adipose tissue
Blood
Fattyacids
Insulin lowGlucagon high
Protein
Aminoacids
GlycogenGlycogen
Glucose
Glucose
Aminoacids
Fattyacids
Glycerol
Triglycerides
LP
Ketones
Ketogenesis Gluconeogenesis
Ketones
Urea
Energy
Glucose-6-phosphate
Low I/G stimulates: 2) adipose lipolysis and liver ketogenesis for glucose sparing
Slide 31
Diabetes Mellitus
High blood glucose deficiency in insulin action
Type 1 : inadequate insulin secretion, insulin-dependent diabetes mellitus (IDDM). Type 2 : a relative lack of response by target tissue cells to insulin, non insulin-dependent diabetes mellitus (NIDDM).
Slide 32
Low level of insulin
10% of all DM
IDDM patients must receive insulin injections..
During adolescence, autoimmune beta cell loss; genetics + environment factor (maybe virus)
Type 1 DM
Slide 33
90% of DM patients has type 2 diabetes.
Insulin-resistant tissues (adipose and muscle); genetics + obesity;
Tx)Diet and losing weightOral hypoglycemics: augmentation of insulin action in tissue.
Type 2 DM
Slide 34
Types 1 and 2: hyperglycemia glucosuria polyuria dehydration
Type 1 (low I/G): ketogenesis ketoacidosis urinary ketones + cations
electrolyte imbalance
Acute complications of diabetes
Slide 35
narrowing of larger vessels in brain, heart, and lower extremities stroke, heart attack or loss of limb;
microvascular lesions nephropathy, retinopathy
Peripheral neuropathy;
sensory dysfunction loss of feeling in lower limb
ANS dysfunction GI, bladder, and impotence,
Chronic complications of diabetes