Metabolism
FOOD
sugars
proteins
fats
amino acids
simple sugars
(glucose)
fatty acids
proteins
glycogen
lipids
glucose
glucose
muscle
glucose
glucose
liver
glucose
fat
Mammalian Pancreas
Gall bladder
liver
Bile Duct
Pancreas
duodenum
-Exocrine Pancreas:
Pancreatic duct
secretes digestive enzymes, alkaline pancreatic fluid
-Endocrine Pancreas:
protein metabolism
secretes hormones that regulate carbohydrate, lipid, and
Endocrine Pancreas
Islets of Langerhans
Exocrine cells
• Islets of Langerhans: 4 cell types
–
–
–
–
 cells: secrete glucagon
 cells: secrete insulin
 cells: secrete somatostatin
F cells: secrete pancreatic polypeptide


capillaries

Pancreatic Hormones
• Insulin
• Glucagon
• Somatostatin
INSULIN
• Regulation of Secretion
– Hyperglycemia stimulates release
• Glucose sensors in  cells
– Gastric Inhibitory Peptide
• Released from cells of the small intestine
• Potent stimulator of insulin secretion
– Somatostatin: inhibits insulin release (paracrine)
– Autonomic nervous system
• Parasympathetic activation increases insulin release
• Sympathetic activation blocks insulin release
• Epinephrine (from adrenal) blocks insulin release
INSULIN
• Action at Target Tissues
– Activation of insulin receptor:
• Increases transport of glucose, amino acids, and fatty
acids into cells
Glucose transporter:
INSULIN
• Action at Target Tissues
– Activation of insulin receptor:
• Increases transport of glucose (glucose transporter),
amino acids, and fatty acids into cells
– Enhancement of anabolic pathways, decrease in
catabolic pathways
– Increases enzymes that activate:
• Glycogen formation (liver)
• Lipogenesis (fat)
• Protein Synthesis (muscle)
Pancreatic Hormones
• Insulin
– Hypoglycemic, glycogenic, lipogenic, anabolic
• Glucagon
• Somatostatin
Glucagon
• Hyperglycemic (increases plasma glucose)
– (one of many in the body)
• Actions at target cells
– Liver
• Promotes glycogenolysis
• Promotes gluconeogenesis
– Fat Tissue
• Promotes lipolysis
Pancreatic Hormones
• Insulin
– Hypoglycemic, glycogenic, lipogenic, anabolic
• Glucagon
– Hyperglycemic, lipolytic
• Somatostatin
– Paracrine agent
– Believed to inhibit insulin and glucagon release
– Inhibits digestion through several pathways
Glucose Regulation

Insulin: decreases blood
glucose levels

Glucagon: increases blood
glucose levels
 Somatostatin: inhibits insulin and
glucagon levels (paracrine) and
digestive processes
DIABETES MELLITUS
• Type 1—juvenile onset—insulin dependent
– IDDM
– Underproduction of insulin
• Type 2—adult onset—non-insulin dependent
– NIDDM
– Insulin receptor resistance
– Post-receptor mechanism problem
Type 1 Diabetes
Insulin Dependent: IDDM
• Likely results from autoimmune reaction
– The body’s immune system attacks the  cells
• Pancreatic  markedly reduced
– Symptoms only appear after ~80% loss of cells
• No insulin……physiological repercussions?
• Treatment
– Insulin injections or insulin pump
– Recent methods
Islet Transplantation
Separate islets from exocrine pancreas
Encapsulate islets (immune protection)
Inside the patient
http://diabetes.niddk.nih.gov/dm/pubs/pancreaticislet/
Inject into liver portal vein
Type 2 Diabetes:
Non-Insulin Dependent: NIDDM
• Accounts for 90-95% of all Diabetes cases
• Usually occurs in overweight individuals
over 40 years of age
– But ages are getting younger and younger
– Associated with abdominal fat in women
• Target cells become resistant to insulin
– insulin receptor
• Fewer receptors
• Receptors have lower affinity
• Receptor blocked (possibly by antibody)
– Post-receptor mechanisms
Diabetes Prevelence in US
%
Incidence of diagnosed diabetes
1980
1990
2000
2007
2004
% of adults >20
2007
New Cases in <20 yrs old
Type 2 Risks 2006
• 7th leading cause of death
• With Type 2 diabetes
– 2 to 4-fold increase in heart disease related death
– 2-fold risk of death
• Type 2 associated complications
–
–
–
–
2-4 fold risk of stroke
75% of adults with Type 2 have high blood pressure
leading cause of blindness in adults aged 20-74
Leading cause of kidney failure