You are on page 1of 41

Pancreatic Hormones & Antidiabetic Drugs

Dr. Meera Ababneh, Pharm.D, PhD

Type of cells Approximate Percent of Islet Mass Hormones secreted

Alpha (A) cell Beta (B) cell Delta (D) cell G cell F cell (PP cell)

20 75 3-5 1 1

Glucagon Insulin, C-peptide, proinsulin, amylin Somatostatin Gastrin Pancreatic polypeptide (PP)

Pancreas Gland
Insulin : storage and anabolic hormone of the body Islet amyloid polypeptide (IAPP, or amylin): modulates appetite, gastric emptying, and glucagon and insulin secretion Glucagon: hyperglycemic factor that mobilizes glycogen stores Somatostatin: a universal inhibitor of secretory cells Gastrin: stimulates gastric acid secretion Pancreatic peptide: facilitates digestive processes by a mechanism not yet clarified.

Pancreatic Endocrine Function

Promotes cell use of glucose and carbohydrate storage (mostly in skeletal muscle) Constantly secreted by the pancreas in response to blood glucose levels Stimulates glycogen synthesis in the liver Facilitates entry of amino acids into the cell

Incretins also stimulate insulin secretion.

Pancreatic Endocrine Function

Increases circulating glucose levels Stimulates glycogenolysis in liver, which allows glucose to enter circulation Also helps in converting amino acids to glucose

Healthy Response
Eat meal, peak glucose at about 30 minutes Phase 1: stored insulin released upon ingestion of meal Glucose continues to rise, reaching above 100mg/dl 20 minutes later Phase 2: beta cells secrete more insulin 1-2 hours later, glucose levels reach around 85 mg/dl

Insulin promotes synthesis

Endocrine effects of insulin (1)

Effect on liver:
Reversal of catabolic features of insulin deficiency Inhibits glycogenolysis Inhibits conversion of fatty acids and amino acids to keto acids Inhibits conversion of amino acids to glucose Anabolic action Promotes glucose storage as glycogen (induces glucokinase and glycogen synthase, inhibits phosphorylase) Increases triglyceride synthesis and very-low-density lipoprotein formation

Endocrine effects of insulin (2)

Effect on muscle:

Increased protein synthesis

Increases amino acid transport Increases ribosomal protein synthesis Increased glycogen synthesis Increases glucose transport Induces glycogen synthase and inhibits phosphorylase

Endocrine effects of insulin (3)

Effect on adipose tissue: Increased triglyceride storage Lipoprotein lipase is induced and activated by insulin to hydrolyze triglycerides from lipoproteins

Glucose transport into cell provides glycerol phosphate to permit esterification of fatty acids supplied by lipoprotein transport Intracellular lipase is inhibited by insulin

Diabetes Mellitus
Disorder of pancreatic endocrine function resulting in:
Deficient secretion of insulin Insulin resistance
The excess production of insulin causes the down regulation (decrease) in the number of receptors and the target cells cannot synthesize enough receptor protein to keep up, further contributing to the problem.

Combination of both

Types of DM
Type 1
Autoimmune disorder (coxsackie virus implicates as trigger) Destruction of beta cells Cessation of insulin production

Type 2
Insulin resistance Obesity Genetic link

Type 3
specific causes of an elevated blood glucose

Type 4
Gestational diabetes (GDM)

Diabetes Mellitus
Symptoms of diabetes: Increased blood glucose levels Glycosuria Polyuria Polydipsia Polyphagia Diabetic neuropathy

Diabetes Mellitius (symptoms cont.)

Ketoacidosistype 1 diabetics
The breakdown of fat produces an increase in ketone bodies in the blood. This condition is called ketosis. As the ketone level increases, metabolic acidosis (ketoacidosis) occurs.

Inadequate circulation to the extremities, coupled with soft-tissue infections that resist healing, may lead to necrosis (gangrene) and the need for amputation.

Diabetes Mellitus
Blood glucose monitoring:
A healthy fasting blood glucose level is between 70 and 110mg/dL. Glucose meters:
Used to test blood glucose levels several times a day

Glycolated hemoglobin (HbA1c):

Used to evaluate 3 months of glucose levels Hemoglobin that has glucose attached to it. Because RBCs do not require insulin to uptake glucose, glucose enters the RBC and readily binds to hemoglobin without the help of enzymes.

Treatment of Diabetes Mellitus

Immediate therapy is to correct metabolic imbalance.

Maintenance therapy is directed at regulating blood glucose levels:

Diet control Exercise Medications

Diabetes Treatment
Parenteral administration:
Insulin, amylin analog, incretin mimetics

Oral antidiabetics
Secretagogues, glucose absorption inhibitors, biguanides, insulin sensitizers, peptidase inhibitors

*insulin and secretagogues are hypoglycemics: decrease normal or elevated glucose levels


Insulin was originally obtained from pork or beef organs.

Today it is produced only through synthesis:

Recombinant DNA technology

Insulin available today comes in different onsets and durations of actions.

Insulin preparation
Rapid-acting Short-acting Intermediate-acting Long-acting Insulin delivery systems

Extent and duration of action of various types of insulin

It is usually administered 30 to 60 minutes before meals.
The long-acting recombinant DNA insulins are dosed once daily. Insulin is administered with a specifically calibrated syringe.

Insulin pens are an alternative for delivering a precise dose.

Changes in insulin requirements:
Colds, fevers, surgery, and stress all increase glucose levels, which increases insulin need.
Heavy exercise can lower the insulin need.

Drugs can affect glucose levels, requiring changes to the insulin dose.
Allergic reactions may necessitate change to another species of insulin. Lipodystrophy is a disappearance of subcutaneous fat at the site of insulin injection.

Adverse effects:
Blurred vision Hypoglycemia Hunger Headache Fatigue Anxiety Nervousness Confusion Paresthesia

Amylin Analogs (sc admin)

It is the hormone co-secreted by the beta cells with insulin. Without enough amylin, blood glucose levels rise. Slows gastric emptying and suppresses glucagon secretion, satiety signal

Pramlintide (Symlin):
Mimics amylin to control glucose levels Adverse effects include vomiting, decreased appetite, headache, and dizziness

Incretin Mimetics
Hormones secreted from the duodenum, due to glucose stimulation Increase insulin secretion
GIP (gastric inhibitory peptide) GLP-1 (glucagon-like peptide-1)

Exenatide(Byetta) and liraglutide(Victoza):

Incretin mimetic Adverse effects include nausea, diarrhea, headache, and dizziness

Oral Antidiabetic Drugs

Used in the management of type 2 diabetes Approved for treatment when diet and exercise have not achieved target glycemic control

Oral Antidiabetic Drugs

Substances that induce or cause the secretion of another substance Enter beta cells and cause the release of insulin Do not have insulin-like activity, so should not be used in type I diabetes

Two generations Reduce fasting plasma glucose

Stimulate insulin secretion Quicker onset of action than sulfonylureas

Both types must be taken 1 to 30 minutes before each meal.

Adverse effects:
Hypoglycemia GI irritation Nausea Diarrhea Weakness Fatigue Dizziness

Glucose Absorption Inhibitors

Interrupt carbohydrate digestion from diet Glucose absorption delayed but not eliminated Keep blood glucose levels from peaking after meals Taken with each meal

Glucose Absorption Inhibitors

Adverse effects:
GI flatulence Diarrhea

Abdominal pain
Do not cause hypoglycemia unless used in combination with secretagogues or insulin

Antihyperglycemic: Biguanides
Decrease blood glucose levels after meals by decreasing liver glucose production and intestinal glucose absorption Enhance glucose use by other tissues in the body No direct effect on insulin secretion

Adverse effects:
Diarrhea Nausea Vomiting Lactic acidosis (rare), life-threatening black box warning

Alcohol potentiates the action of metformin on lactic acid metabolism

Insulin Sensitizers: Thiazolidinedione

Enhance peripheral cell response to insulin Allow glucose to be used more efficiently Decrease insulin resistance and increase insulin sensitivity of fat, skeletal muscle, and liver cells

Insulin Sensitizers
Adverse effects:
Fluid retention
Weight gain

Fatigue Diarrhea Contraindicated liver and cardiovascular disease states.

Dipeptidyl Peptidase-4 Inhibitors

DPP-4 in intestine
Breaks down GLP-1

Inhibitor leads to:

Stimulation of insulin secretion Decreased glucagon secretion

Adverse effects:
Nasopharyngitis Upper respiratory infections Headache