Insulin, Oral Hypoglycemics, and Glucagon

Proinsulin is made of what?

A chain, B chain, C Chain

How is insulin broken down when it is processed?

A and B linked by disulfide, C is cleaved and has no known function

Insulin degradation time

t1/2= 3-5 min

Pancreatic cells that make insulin

Beta cells

Insulin is released as a complex with __ insulin molecules and what else?

6 insulin, 1 Zinc

Blood glucose levels serve as a surrogate for what?

Insulin action

Physiological roles of insulin

1. Increased glycogen synthesis

2. glucose uptake

Differences in ethnic percentages of risk are determined by genetic or socioeconomic factors?

Socioeconomic

T2 Diabetes treatment

Secrete more insulin, restore sensitivity, reduce blood glucose from diet.

Meglitinides (Repaglinide) MOA

• Regulate K+ flux through K channels

• Overlap with sulfonylureas on binding site

• Rapid onset of action — peak at 1 hr

  (Favorable pharmokinetics = fast onset)

Metformin (Glucophage) MOA

Inhibits liver gluconeogenesis, directly stimulating glycolysis.

Two Thiazolinediones

Rosiglitazone and Pioglitazone

Thiazolinediones MOA

Acute post-receptor mimetic activity. Chronic effects of transcription of genes of glucose and lipid metabolism via PPAR nuclear receptor.

Two Alpha-Glucosidease inhibitors

Acarbose (Precose), Miglitol (Glyset)

Alpha-glucosidase Inhibitors MOA and side effects

Competitive inhibitor of intestinal a-glucosidase. Side effect = GI distress

Exenatide MOA

bind GLP-1 receptors not degraded by DPP-4

Sitagliptin MOA

Inhibit DPP-4

Popular Incretin Related Drugs

Ozempic and Wegovy (Semaglutides)

Amylin analog given by injection at mealtimes

Pramlintide

Cangliflozin inhibits what?

SLGT-2 to prevent glucose re-absorption

Glucagon secreted by what cells and function

A cells of pancreas, counteract insulin. Converts glycogen storage to glucose

Type 1 treatment strategy

Replace insulin synthetically

Clinical uses of glucagon

• Treatment of hypoglycemia

• Diagnosis of endocrine disorders

• B-Blocker poisoning

• Radiology of the bowel

Ultra short acting insulins

Insulin Lispro (Humalog), Aspart insulin (Novalog)

Insulin type that decreases the ability of insulin to form hexamers.

Ultra short acting

Short acting insulin drugs

Regular Human insulin

Short acting (regular) insulin MOA

Short acting, soluble zinc insulin. Effective 30 min after injection, only form administered by IV.

Intermediate and Long acting insulin names

NPH, Humulin N, Novolin N, Lente insulin, Humulin L, Novolin L. Ultralente Insulin, Glargine (Lantus)

Intermediate and long acting Effects

Bioengineered, has a rapid onset and prolonged action. Protamine and insulin mix, allows for breakdown over time.