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