Chapter 31: Insulin, Oral Hypoglycemics, and Glucagon
The endocrine system of the pancreas comprises the (...), which contain four types of cells that synthesize and secrete different polypeptide hormones

islets of Langerhans
Insulin is produced by the (...), which constitute most of the islet and form its central core.
β cells
Insulin is composed of two (...) joined by two (...).
chains (A and B); disulfide bridges
Proinsulin is converted to insulin when the (...) is removed, which occurs within the secretory granules of the pancreatic β cell.

C peptide
C peptide has no known biologic function, but it can serve as an (...).
index of insulin secretion
Insulin is a member of a family of related peptides known as (...).
insulin-like growth factors (IGFs)
(...) is the principal stimulus to insulin secretion in humans.
glucose
The classic action of insulin is to (...).
decrease the blood glucose concentration
Insulin decreases the blood glucose production by increasing glucose (...), increasing glucose (...), and decreasing glucose (...).
uptake; utilization; production
The important target tissues for regulation of glucose homeostasis by insulin include (...) cells.
liver, muscle, and fat
Insulin affects the activities of various enzymes involved in intracellular use and storage of (...).

glucose, amino acids, and fatty acids
Insulin may be given (...).
subcutaneously, intravenously, or intramuscularly
Endogenous insulin is secreted into the (...) circulation; injected insulin is delivered into the (...) circulation.
portal; peripheral
The insulin receptor is composed of two (...) and two (...) linked by (...).

α subunits; β subunits; disulfide bonds
There is evidence that insulin acts by synthesis of second messengers of the (...) class.
inositolphosphoglycan (IPG)
(...) is a group of syndromes characterized by hyperglycemia.
diabetes mellitus
Virtually all forms of DM are due to either a decrease in the (...) or a decrease in the (...).
concentration of insulin (insulin deficiency); response to insulin (insulin resistance)
(...), occurs during pregnancy and resolves after parturition, but is important because it is a predictor of future risk of diabetes.
gestational diabetes
(...) is an autoimmune disease of the pancreatic β cell, resulting in degeneration and an absolute lack of insulin.
type 1 diabetes
In (...), impaired glucose metabolism in muscle and liver results in relative insensitivity to insulin.
type 2 diabetes
At elevated blood glucose concentrations, hemoglobin is glycosylated on its amino terminal valine residue to form the glycosyl valine adduct, termed (...).
hemoglobin A1c (HbA1c)
Because the half-life of HbA1c is the same as that of (...), its concentration can be used to assess the severity of the glycemic state over the previous (...).

red blood cells; 8 to 12 weeks
Type 1 diabetes mellitus must be treated with (...); type 2 diabetes mellitus may be treated with a combination of (...).
insulin; diet and exercise, oral antihyperglycemic agents, or insulin
(...) insulin analogues have amino acids are substituted, or reversed.
ultrashort-acting
List the ultrashort-acting insulin preparations. (3)
- aspart
- glulisine
- lispro
(...) insulins are short-acting preparations.
regular
List the regular, short-acting insulin preparations. (2)
- humulin R
- novolin R
The intermediate-acting (...) insulin preparations contain particles and are cloudy suspensions at neutral pH.
NPH
List the intermediate-acting, NPH insulin preparations. (2)
- humulin N
- novolin N
(...) insulin analogues have groups added to alter their kinetics.
long-acting
List the long-acting insulin preparations. (3)
- glargine
- detemir
- degludec
Most commercial preparations of insulin are supplied in solution at a concentration of (...).
100 units/mL (approximately 3.47 mg/mL)
Insulin absorption is usually most rapid from the (...), followed by the arm, buttock, and thigh.
abdominal wall
(...) is the most common adverse reaction to insulin.
hypoglycemia
List the symptoms of hypoglycemia. (8)
- sweating
- tachycardia
- tremor
- blurred vision
- weakness
- hunger
- confusion
- altered behavior
What class of drug are the following?
- chlorpropamide
- tolazamide
- glimepiride
- glipizide
- glyburide
sulfonylureas
Sulfonylureas are effective only in patients with (...).
functioning pancreatic β cells
Sulfonylureas stimulate release of insulin by blocking (...) in pancreatic β cells.
ATP–dependent K+ current
Sulfonylureas have a (...) structure, which is the basis for (...) with certain antibacterial drugs.

sulfonamide; cross-sensitivity
List the adverse effects of sulfonylureas. (7)
- hypoglycemia
- hypersensitivity reactions
- naseua and vomiting
- hematologic reactions
- cholestatic jaundice
- dermatologic effects
- weight gain
List some drugs that increase the effect of sulfonylureas. (6)
- antihistamines
- azole antifungals
- oral anticoagulants
- salicylates
- Sulfonamides
- β-Adrenergic receptor blockers
List some drugs that decrease the effect of sulfonylureas. (6)
- Ca2+ salts
- corticosteroids
- estrogens
- sympathomimetics
- thiazide diuretics
- thyroid hormones
Sulfonylureas cause a (...) effect by decreasing the activity of aldehyde dehydrogenase.
disulfiram-like
What class of drug are the following?
- repaglinide
- nateglinide

meglitinides
Meglitinides are effective only in patients with (...).
functioning pancreatic β cells
Meglitinides stimulate release of insulin by blocking (...) in pancreatic β cells.
ATP-dependent K+ channels
(...) is the major adverse effect of repaglinide and is most likely to occur if a meal is delayed or skipped or in patients with hepatic insufficiency.
hypoglycemia
Drugs that inhibit (...) may potentiate the effect of nateglinide.
cytochrome p450 (e.g. fluconazole, amiodarone)
(...) drugs may potentiate the hypoglycemic effects of repaglinide.
nonsteroidal antiinflammatory drugs
(...) is currently the only biguanide approved for use in the United States.

metformin
Biguanides stimulate (...) thereby decreasing blood glucose concentrations by several different actions.
AMP-activated protein kinase (AMPK)
Unlike sulfonylureas and meglitinides, biguanides do not cause (...) or (...) and do not depend on (...).
hypoglycemia; weight gain; functioning pancreatic β cells
List the common adverse effects of metformin. (6)
- nausea
- anorexia
- vomiting
- diarrhea
- flatulence
- cramps
Metformin may cause a decrease in vitamin (...) levels, possibly by decreasing absorption.
B12
(...) is a rare but serious complication of biguanides that is fatal in roughly 50% of patients in which it occurs.
lactic acidosis
Biguanides are contraindicated in patients with renal disease, hepatic disease, or conditions predisposing to tissue anoxia because of concern regarding (...).
lactic acidosis
What class of drug are the following?
- pioglitazone
- rosiglitazone

thiazolidinediones
Thiazolidinediones act by increasing insulin sensitivity in tissues by acting on (...).
nuclear peroxisome proliferator-activated receptor-γ (PPARγ)
The thiazolidinediones depend on (...) for their activity.
presence of insulin
Thiazolidinediones now carry a “black box” warning of (...).
congestive heart failure and myocardial ischemia
(The risk is greater with rosiglitazone.)
List the adverse effects of thiazolidinediones. (6)
- congestive heart failure
- myocardial ischemia
- weight gain
- edema
- osteoporosis
- hepatotoxicity
Pioglitazone can decrease the plasma concentration of (...).
oral contraceptives
Hormones secreted from the gastrointestinal tract that have been shown to stimulate insulin secretion are known as (...).
incretins
(...) is an incretin that has been shown to augment glucose-dependent insulin secretion.
glucagon-like peptide 1 (GLP-1)
GLP-1 is rapidly inactivated by (...).
dipeptidyl peptidase 4 (DPP-4)
Incretin-related drugs that act by either stimulating (...) or inhibiting (...).

GLP-1; DPP-4
What class of drug are the following?
- exenatide
- albiglutide
- dulaglutide
- liraglutide
GLP-1 receptor agonists
What class of drug are the following?
- sitagliptin
- saxagliptin
- linagliptin

DPP-4 inhibitors
What class of drug are the following?
- canagliflozin
- dapagliflozin
- empagliflozin

SGLT2 inhibitors
The SGLT2 inhibitors block (...) which facilitates (...) in the kidney.
sodium-glucose co-transporter 2; glucose reabsorption
List the adverse effects of SGLT2 inhibitors. (5)
- urinary tract infections
- increased urinary urgency
- hypotension
- bladder cancer
- hyperkalemia
(This class of drugs is not indicated for type 1 diabetics)
(...) is a peptide produced by pancreatic β cells and cosecreted with insulin that has a role in the maintenance of glucose homeostasis.
amylin
(...) is an analogue of amylin that is approved in the United States.
pramlintide
(...) facilitate digestion of complex starches, oligosaccharides, and disaccharides into monosaccharides, allowing them to be absorbed from the small intestine.
α-glucosidases
What class of drug are the following?
- acarbose
- miglitol

α-glucosidase inhibitors
α-glucosidase inhibitors are competitive, reversible inhibitors of intestinal (...), which delays (...).
α-glucosidases; absorption of carbohydrates
List the adverse effects of α-glucosidase inhibitors.
- flatulence
- diarrhea
- abdominal pain
- hypoglycemia*
*with concurrent sulfonylurea therapy
The gastrointestinal adverse effects of α-glucosidase inhibitors are due to (...).
undigested carbohydrates in the lower gastrointestinal tract
Treatment of hypoglycemia in patients taking α-glucosidase inhibitors should be with (...), because breakdown of (...) may be inhibited.
glucose; sucrose
Evidence suggests that interaction of insulin with its receptor leads to the release of (...), which enter the cell and act as mediators of insulin action.
IPGs
(...) and (...) have been shown to delay the onset and reduce significantly the progression of diabetic nephropathy.
ACE inhibitors; angiotensin II receptor blockers
(...) is synthesized in the α cells of the pancreatic islets.
glucagon
Glucagon increases blood glucose concentration by decreasing (...), stimulating (...), and increasing (...) in the liver.
glycogenesis; glycogenolysis; gluconeogenesis
Glucagon may be given parenterally in the emergency treatment of (...).
severe hypoglycemic reactions (sufficient to cause unconsciousness)
Major risk factors for type 2 diabetes are (...) and (...).
obesity; physical inactivity
List the oral complications of diabetes.
- oral paresthesias (e.g. burning mouth)
- increased susceptibility to infection
- delayed wound healing
- xerostomia
- increased incidence and severity of caries
- periodontal disease
- periapical abscesses
Morning appointments are usually better for diabetic patients because that minimizes the chance of (...).
stress-induced hypoglycemia
Since (...) may cause an increase in blood glucose levels, short appointments may be helpful in preventing an increase in blood glucose levels.
stress
It is suggested that the patient’s blood glucose should be less than (...) before any invasive therapy is started.
200 mg/dL
Use of local anesthetic with (...) may cause transient hyperglycemia.
epinephrine
(...) drugs have the potential to raise blood glucose levels.
glucocorticosteroid

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