• Inhibits release of insulin via Alpha2 Adrenoceptors 
• Promotes glycogenolysis via Beta2 Arenoceptors in striated muscle and liver

1. Gastrointestinal Inhibitory Peptide (GIP)
2. Glucagon-Like Peptide 1 (GLP-1)
3. Gastrin
4. Secretin
5. Cholecystokinin
6. Vasoactive Intestinal Peptide
7. Gastrin-Releasing Peptide
8. Enteroglucagon

GLUT-2 receptors are expressed:

1. in muscle tissues
2. in fat tissues
3. in the liver
4. in pancreatic beta cells
5. 3 and 4

GLUT-4 receptors are expressed:

1. in muscle tissues
2. in fat tissues
3. in the liver
4. in pancreatic beta cells
5. 1 and 2

GLUT-4 receptors are expressed in:

1. skeletal muscle tissues
2. fat tissues
3. heart

1. Coxsackievirus B
2. Rubella Virus
3. Rotavirus
4. Mumps Virus

• Monoclonal Antibody (Phase III)
• Used as an immunosuppressive drug (anti-CD3)
• May preserve pancreatic cell function

• Rapid Acting Insulin
• Exists as a hexamer but instantaneously dissociates into monomers following injection
• More rapid absorption and shorter duration of action compared to regular insulin

• Rapid Acting Insulin
• Used for continuous subcutaneous insulin infusion pump use

• Rapid Acting Insulin
• Similar effects on glucose control and hypoglycemia frequency with insulin aspart and lispro

Intermediate Acting Insulin

(Humalin-N, Novolin-N)

• Formulated to dissolve more gradually when administered subcutaneously
• Usually given once a day before breakfast or 2x a day

Long Acting Insulin

• A clear sol'n with a pH of 4.0 --> therefore, cannot be mixed with other short acting insulins preparations
• Does not accumulate with multiple injections
• can be combined with oral antihyperglycemic meds
• site of administration does not influence the time-action profile of glargine
• exercise does not influence glargine's unique absorption kinetics

Results in:

• less hypoglycemia
• has sustained peakless profile
• provides better once daily 24 hrs insulin coverage than NPH

Long Acting Insulin

Reversibly bound to plasma albumin

Allows for protracted duration of effect via delayed absorption due to albumin binding in subcutaneous adipose tissue and plasma

1. Enhanced insulin secretion (secretagogue)

binds to SUR-1 on beta cells --> closes Kir 6.2 K+ channels --> K+ cannot efflux and depolarization occurs --> opens voltage gated Ca2+ channels and Ca2+ goes into the cell --> results in exocytosis of insulin from vesicles

2.  Reduces serum glucagon

3.  Increases insulin binding to receptors

1. Hypoglycemia
2. Hyponatremia - Chlorpropamide has the action of an antidiuretic hormone on the distal tubule of nephrons
3. Weight gain

1. Tolbutamide
2. Acetohexamide
3. Chlorpropamide
4. Tolazamide

1. Glipizide
2. Glimepiride
3. Glyburide

1. Alpha2 Adrenergic Antagonists
2. GLP-1
3. Exenatide
4. PDE Inhibitors

1. Sulfonylureas - long acting insulin secretagogue
2. Repaglinide - short acting insulin secretagogue
3. Nateglinide - short acting insulin secretagogue

Repaglinide, Nateglinide

• Similar to SUs, acting on the SUR-1 on KATP channels in pancreatic Beta cell membrane
• Less potent than most SU's
• Rapid absorption and elimination - lower risk of hypoglycemia
• Administered shortly before meals to reduce glucose rise in patients with Type 2 DM

1. Reduces hepatic glucose output
2. Decreases absorption of glucose from the gut
3. Increases insulin sensitivity in peripheral tissues
4. Improves glucose utilization and uptake in skeletal muscles and adipose tissues
5. Reduces hyperlipidemia

1. Lactic acidosis - in patients with liver disease, surgery, myocardial infarctions, CHF
2. Taste Aversion
3. GI effects - diarrhea, irritation

PPAR-γ Agonists

Rosiglitazone, Pioglitazone

• Activate insulin-responsive genes that regulate carbohydrate and lipid metabolism
• Depend on the presence of insulin for their activity
• Increase glucose uptake by skeletal muscles
• Decrease hepatic glucose production
• Facilitate distribution of fat from liver and skeletal muscle to adipocytes
• Results in maturation of preadipocytes to mature adipocytes

1. Liver abnormalities - do not start agent when 2.5X ULN, discontinue agent when 3.0X ULN
2. Edema - CI in patients with NYHA III-IV, caution the use of Rosiglitazone in patients with NYHA I-II
3. Dose-related Weight Gain
4. Ovulation
5. Macular Edema
6. Fractures

Reversible Inhibitors of Intestinal Alpha-Glucosidase

Acarbose, Miglitol

• Reduces intestinal absorption of starch, dextrin, and disaccharides
• Slows absorption of carbs
• Reduces postprandial increases in blood glucose

1. GI - flatulence, bloating, diarrhea
2. Liver abnormalities - CI in patients with inflammatory bowel disease, short-bowel syndrome, other bowel obstruction histories

• Significantly augments glucose-dependent insulin secretion
• Reduces glucagon secretion
• Increases the number of beta-cells
• Delays stomach emptying

• Significantly augments glucose-dependent insulin secretion
• Reduces glucagon secretion
• Increases the number of beta-cells
• Delays stomach emptying

GLP-1 Agonist (Incretin Mimetic)

• Mimics the enhancement of glucose-dependent insulin secretion (through cAMP mechanisms)
• Inhibits glucagon secretion
• Slows GER
• Possibly Beta-cell proliferation
• Not degraded by DPP-IV
• Helps restore first phase insulin release
• Injectable

1. Hypoglycemia
2. GI - nausea/vomiting, pancreatitis, CI in patients with severe GI disease
3. Kidney insufficiency - do not use if CrCl < 30 mg/dL
4. Weight loss

Pramlintide

• Suppression of post-meal glucagon secretion
• Centrally-mediated modulation of appetite
• Slowing of GER without altering the overall absorption of nutrients
• Used in conjunction with insulin therapy