Page 761 - Basic _ Clinical Pharmacology ( PDFDrive )

C H A P T E R

Pancreatic Hormones & 41

Antidiabetic Drugs

Martha S. Nolte Kennedy, MD, &
Umesh Masharani, MBBS, MRCP (UK)

C ASE STUD Y

A 66-year-old obese Caucasian man presented to an 4 times a day. He was smoking half a pack of cigarettes a day.
academic Diabetes Center for advice regarding his diabetes On examination, his weight was 132 kg (BMI 39.5); blood
treatment. His diabetes was diagnosed 10 years previously pressure 145/71; and signs of mild peripheral neuropathy
on routine testing. He was initially given metformin but were present. Laboratory tests noted an HbA1c value of
when his control deteriorated, the metformin was stopped 8.1%, urine albumin 3007 mg/g creatinine (normal <30),
and insulin treatment initiated. The patient was taking serum creatinine 0.86 mg/dL (0.61–1.24), total choles-
50 units of insulin glargine and an average of 25 units of terol 128 mg/dL, triglycerides 86 mg/dL, HDL cholesterol
insulin aspartate pre-meals. He had never seen a diabetes 38 mg/dL, and LDL cholesterol 73 mg/dL (on atorvastatin
educator or a dietitian. He was checking his glucose levels 40 mg daily). How would you treat this patient?

■ THE ENDOCRINE PANCREAS ■ INSULIN

The endocrine pancreas in the adult human consists of approxi- Chemistry
mately 1 million islets of Langerhans interspersed throughout
the pancreatic gland. Within the islets, at least five hormone- Insulin is a small protein with a molecular weight in humans of
producing cells are present (Table 41–1). Their hormone products 5808. It contains 51 amino acids arranged in two chains (A and
include insulin, the storage and anabolic hormone of the body; B) linked by disulfide bridges; there are species differences in the
islet amyloid polypeptide (IAPP, or amylin), which modulates amino acids of both chains. Proinsulin, a long single-chain protein
appetite, gastric emptying, and glucagon and insulin secretion; molecule, is processed within the Golgi apparatus of beta cells and
glucagon, the hyperglycemic factor that mobilizes glycogen packaged into granules, where it is hydrolyzed into insulin and a
stores; somatostatin, a universal inhibitor of secretory cells; pan- residual connecting segment called C-peptide by removal of four
creatic peptide, a small protein that facilitates digestive processes amino acids (Figure 41–1).
by a mechanism not yet clarified; and ghrelin, a peptide known Insulin and C-peptide are secreted in equimolar amounts
to increase pituitary growth hormone release. in response to all insulin secretagogues; a small quantity of

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