Endocrine Pancreas and Diabetes Mellitus

Study Notes

Produces hormones: Insulin, Islet Amyloid Polypeptide (IAPP), Glucagon, Somatostatin, Gastrin, and Pancreatic Peptide

Defined as elevated blood glucose associated with inadequate insulin secretion or function
Classified into four types:
- Type 1 (Insulin-dependent)
- Type 2 (Non-insulin-dependent)
- Type 3 (Other causes, like pancreatectomy)
- Type 4 (Gestational)

Characterized by beta cell destruction and severe insulin deficiency
Most common cause is immune-mediated, but can also be idiopathic
Majority of patients are diagnosed before 30 years old, but onset can occur at any age
Requires insulin replacement therapy for survival

Marked by tissue resistance to insulin action and relative insulin deficiency
Approximately 10-20% of individuals diagnosed with type 2 may actually have both type 1 and type 2, or latent autoimmune diabetes of adults (LADA), eventually requiring full insulin replacement

Small protein with a molecular weight of 5808 in humans
Consists of two chains (A and B) linked by disulfide bridges
Proinsulin, a single-chain precursor, is processed within beta cell Golgi apparatus into insulin and C-peptide
Human pancreas contains up to 8 mg of insulin, equivalent to 200 biologic units

Released from pancreatic beta cells at a basal rate and at a stimulated rate in response to various stimuli, including glucose
Stimulated by sugars (mannose), amino acids (leucine, arginine), hormones (GLP-1, GIP, glucagon, cholecystokinin), fatty acids, and sympathetic activity
Stimulated by drugs: sulfonylureas, meglitinides, GLP-1 receptor agonists, DPP-4 inhibitors, and acetylcholine
Inhibited by: insulin itself, leptin, alpha-adrenergic activity, chronically elevated glucose, and low fatty acids
Inhibited by drugs: diazoxide, phenytoin, vinblastine, and colchicine

Liver and kidney are the main organs responsible for insulin removal from circulation
Liver removes 60% in normal individuals, kidney removes 35-40%
In insulin-treated diabetics, this ratio is reversed, with the kidney clearing up to 60% and the liver clearing 30-40%

Classified by onset and duration of action:
- Rapid-acting (fast onset, short duration)
- Short-acting (rapid onset)
- Intermediate-acting
- Long-acting (slow onset)

Rapid-acting and short-acting insulin are clear solutions with small amounts of zinc for stability
Intermediate-acting NPH insulin is a turbid suspension with protamine in phosphate buffer