Post on 21-Dec-2015
MetabolismFOOD
proteinssugars
fats
amino acids fatty acidssimple sugars(glucose)
muscle
proteins
liver
glycogen
fat
lipids
glucose
glucose glucose
glucose
glucose
Mammalian PancreasGall bladder
duodenum
liver
Bile Duct
Pancreas
Pancreatic duct
-Exocrine Pancreas: secretes digestive enzymes, alkaline pancreatic fluid
-Endocrine Pancreas: secretes hormones that regulate carbohydrate, lipid, and protein metabolism
Endocrine Pancreas
• Islets of Langerhans: 4 cell types cells: secrete glucagon cells: secrete insulin cells: secrete somatostatin
– F cells: secrete pancreatic polypeptide
Islets of Langerhans
Exocrine cells
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 DiabetesInsulin 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
Inside the patient
Separate islets from exocrine pancreasEncapsulate islets (immune protection)
Inject into liver portal veinhttp://diabetes.niddk.nih.gov/dm/pubs/pancreaticislet/
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
2007
2004
% of adults >20
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