Most important stimulus for insulin release

Modulators of Insulin Release

• Amino acids (esp gluconeogenic amino acids, eg. Leucine, Arginine)

• Glucagon-like polypeptide-1 (GLP-1)

• Glucose-dependent insulinotropic polypeptide (GIP)

Modulators of Insulin Release

• Glucagon

• Cholecystokinin

• High concentrations of fatty acids

• b-adrenergic sympathetic activity

Modulators of Insulin Release

• Insulin itself

• Somatostatin

• Leptin

• α-adrenergic sympathetic activity

Modulators of Insulin Release

• Chronically elevated glucose

• Low concentrations of fatty acids

Modulators of Insulin Release

• Diazoxide

• Phenytoin

• Vinblastine

• Colchicine

Insulin Degradation

(1) ________ normally clears the blood of approximately 60% of the insulin released from the pancreas

(2) ________ removes 35-40% of the endogenous hormone

*In insulin-treated diabetics receiving subcutaneous insulin injections, the ratio is REVERSED

Insulin Degradation

t ½ of circulating insulin

Endocrine Effects of Insulin

• _____ glycogenolysis

• _____ conversion of fatty and amino acids to keto acids

• _____ conversion of amino acids to glucose

Endocrine Effects of Insulin

• _____ glucose storage as glycogen (glucokinase and glycogen synthase)

• _____ triglyceride synthesis and very-low-density lipoprotein formation

Endocrine Effects of Insulin

• _______ protein synthesis

• _______ glycogen synthesis

Endocrine Effects of Insulin

_______ triglyceride storage

Endocrine Effects of Insulin

Intracellular lipase is _______ by insulin

Short-acting Insulin Preparations

• Short-acting, soluble crystalline zinc insulin

• Hypoglycemic effect appears within 30 mins after SQ injection

Short-acting Insulin Preparations

• More rapid onset of action

Long-acting Insulin Preparations

• Intermediate-acting insulin

Long-acting Insulin Preparations

• “Peakless”, long-acting insulin analog

Long-acting Insulin Preparations

• supplements of rapid or short-acting insulin before meals

Insulin Delivery

• Facilitate multiple SQ injections of insulin

• Also available for selected formulations

• Contain cartridges of insulin and replaceable needles

Insulin Delivery

• External open-loop pumps for insulin delivery

• Have a user-programmable pump that delivers individualized basal and bolus insulin replacement doses based on blood glucose self-monitoring results.

Insulin Delivery

• Normally, the 24-hour background basal rates are preprogrammed and relatively constant from day to day, although temporarily altered rates can be superimposed to adjust for a short-term change in requirement.

Insulin Delivery

• Dry powder formulation of recombinant regular insulin (technosphere insulin, Afrezza)

• Peak levels: 12 -15 minutes

• Decline to baseline in 3 hours

• Significantly faster in onset and shorter in duration

Insulin Delivery

• Most common adverse effect: Cough

• Can irritate the airway causing bronchospasm

• Pulmonary function should be monitored

• Contraindicated in smokers and patients with chronic obstructive pulmonary disease

Insulin Regimens

• Current regimens

• More predictable

Insulin Regimens

• Multiple daily injections (MDI)

• Long-acting insulin analogs to provide basal or background coverage

• Rapid-acting insulin analogs to meet the mealtime requirements

• Given as supplemental doses to correct transient hyperglycemia

Insulin Regimens

• Half of the computed total daily requirement covers total daily requirement or basal insulin requirement

• Remainder: covers meal and snack requirement and high blood glucose corrections

• Most sophisticated: delivers rapid-acting insulin analogs through a continuous subcutaneous insulin infusion device

Insulin Regimens

• Usually prescribed for certain patients with type 2 DM who are felt not to benefit from intensive glucose control.

• Fixed dose intermediate or long acting

• Short or rapid acting based on plasma glucose

Conditions and Insulin Requirement

• Newly diagnosed with ongoing endogenous insulin requirement

• Long standing DM with insulin sensitivity

Conditions and Insulin Requirement

• Significant renal insufficiency

• Other endocrine deficiencies

Conditions and Insulin Requirement

• Obesity

• Adolescent

Conditions and Insulin Requirement

• Late trimesters of pregnancy

• Type II DM

Clinical Uses of Insulin

• Due to inadequate or absent insulin replacement

• Occurs in people with DM1 (infrequently: DM2)

• Typically occurs in newly diagnosed DM1 patients or in those who have experienced interrupted insulin replacement

• Management: Regular Insulin (IV)

Clinical Uses of Insulin

• Diagnosed in persons with type 2 diabetes

• Characterized by profound hyperglycemia and dehydration

• Management: Low-dose insulin