Insulin - anabolic Glucagon - catabolic

Type 1 DM Treatments 21 res. A-pep+30 res. B-pep 21 residue peptide

Insulins Composition Absorbtion Secreted by B cells w/ C-pep Secreted by a cells
cellular glucose uptake Used to treat insulin
Soluble monomeric rapid gluconeogenesis and glycogenolysis overdose
NPH protamine mix intermediate fatty acid and TG synthesis
Lente Amorphous insulin-zinc suspension slow lipolysis, protein syn.

Ultralente insulin-zinc very slow Insulin Receptor 22 configuration. = insulin binding, = TK

mutated B chain, causing decreased self Insulin Synthesis Initial translation product has N-terminal signal,
Lispro/aspart association. very fast which is removed upon ER insertion. C peptide is cleaved out in
golgi.
mutations, causing precipitation at Secretion: blood glucose cell uptake/catabolism ATP
Glargine injection site ultra long acting ATP-sensitive K+ channel closure depolarization opening
inhaler. Contraindicated in smokers or of voltage sensitive Ca+ channel exocytotic release of insulin.
EXUBERA lung disease rapid Metabolism: Extensive first pass met. So liver sees higher
concentration than other tissues.
Type 2 DM Treatments
Drug Mechanism Pharmacokinetics Clinical use Adverse reactions
~Effective GI abs., end up mostly bound to albumin
1st gen Risk of inducing severe
Tolbutamide: 4-7 hr t1/2 hypoglycemia
Stimulation of insulin release Chlorpromamide: 24-48 hr t1/2
from the pancreas, via reduced 2nd gen Appetite stimulants obesity
conductance through ATP Glyburide/glipizide: 2-4 hr t1/2 Primary agents, in combo with
sensitive K+ channels. Requires ~ Yet, effects from one does last 24- dietary control. High failure rate (7%) prob due
Sulfonylureas functional B cells. 48 hr. 100X more potent than 1st gen. Oral administration to pancreatic insuff.
Glinides Induce insulin secretion through Taken orally at mealtimes to reduce
Repaglinide + closure of the ATP sensitive K+ Very rapid acting, short duration. post-prandial peak. Flexible dosing Less potential for hypoglycemia
Nateglinide channel. depending on meals. since short acting.
Metformin reduces blood Lactic acidosis much less
glucose via unknown common than with phenformin
mechanism. 2 actions: reduced (off market)
liver gluconeogenesis, reduced Often given synergistically with No hypoglycemia
Biguanides insulin resistance. Oral administration sulfonylureas Anorexia
Agonistic binding to PPAR, to Not recommended for first line
Glitazones suppress resistin release from Low incidence of liver tox.
(TZDs) white adipocytes. When used, monthly liver tests.
Induces insulin release Nausea, which often goes away
Glucagon-like-peptide homolog, Depresses glucagon release Twice daily injections with persistant use
derived from gila monster Delays gastric emptying Approved as combo with metformin Increased risk of hypoglycemia if
Exenatide salivary glands Net result: significant weight loss (good!) and sulfonylureas used with sulfonylureas
-glucosidase Not effective as primary therapy
inhibitors Slow intestinal degradation of used with other oral agents when
(acarbose, complex carbs to reduce glucose failure to adequately control post-
miglitol) absorbtion/ prandial glucose levels Flatulence, diarrhea
ALL of the oral anti-diabetics depend on endogenous insulin production. If insulin production is insufficient, need Type 1 DM drugs
Only have risk of hypoglycemia if you are increasing insulin levels in the blood.