Endocrine System: Insulin and Glucose Regulation

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Questions and Answers

What is the current basis for defining the unit of insulin?

Mechanism of insulin release

Weight (correct)

Assay purposes

Purification techniques

What happens to ATP-dependent potassium channels in response to hyperglycemia?

They open

They close (correct)

They are destroyed

They remain unchanged

What is the effect of decreased outward potassium efflux on the beta cell?

Hyperpolarization

Depolarization (correct)

Apoptosis

No change

What is the stimulus for insulin secretion from pancreatic beta cells?

Glucose, amino acids, hormones, and fatty acids Signup and view all the answers

What percentage of insulin is cleared by the liver?

60% Signup and view all the answers

What is the half-life of circulating insulin?

3-5 minutes Signup and view all the answers

What is the normal range of basal serum insulin values?

5-15 μU/mL Signup and view all the answers

What happens to insulin after it enters the circulation?

It diffuses into tissues and binds to specialized receptors Signup and view all the answers

What are the three peptide hormones produced by the pancreas?

Insulin, glucagon, and somatostatin Signup and view all the answers

What is the effect of a lack of insulin in diabetes mellitus?

Hyperglycemia Signup and view all the answers

What is the purpose of administering insulin preparations or other glucose-lowering agents?

To reduce morbidity and mortality associated with diabetes Signup and view all the answers

What is the structure of insulin?

A small protein with 51 amino acids arranged in two chains (A and B) linked by disulfide bridges Signup and view all the answers

What is the function of insulin in the target tissues?

To store energy from glucose and fat Signup and view all the answers

What is proinsulin processed into within the Golgi apparatus of beta cells?

Insulin and C-peptide Signup and view all the answers

What is the effect of glucocorticoids on insulin receptors?

Decrease the affinity for insulin Signup and view all the answers

What is the form in which insulin is stored in granules within beta cells?

Crystals consisting of two atoms of zinc and six molecules of insulin Signup and view all the answers

What is the amount of insulin in the entire human pancreas?

Up to 8 mg Signup and view all the answers

What is the result of aberrant serine and threonine phosphorylation of insulin receptor β subunits or IRS molecules?

Insulin resistance and functional receptor down-regulation Signup and view all the answers

What was the original basis of defining the unit of insulin?

On the basis of the hypoglycemic activity of insulin in rabbits Signup and view all the answers

What is the projected number of people affected by diabetes worldwide by 2030?

350 million Signup and view all the answers

What is the primary cause of type 1 diabetes?

Selective B cell destruction Signup and view all the answers

What is the classification of diabetes with genetic defects or medications?

Other cause Signup and view all the answers

What is the characteristic of immune-mediated type 1 diabetes?

Presence of multiple antibodies Signup and view all the answers

What is the classical symptom of type 1 diabetes?

Polydipsia, polyphagia, polyuria, and weight loss Signup and view all the answers

What level of urinary ketones requires hospitalization?

A level >3.0 mmol/L Signup and view all the answers

What is the purpose of self-monitoring of blood glucose?

To achieve tight metabolic control Signup and view all the answers

What is the function of continuous glucose monitoring (CGM) systems?

To measure glucose concentrations in the interstitial fluid Signup and view all the answers

What is the purpose of a glucose pump?

To automatically deliver insulin Signup and view all the answers

When is regular insulin administered intravenously?

During a hyperglycemic emergency Signup and view all the answers

How is human insulin produced?

Through recombinant DNA technology Signup and view all the answers

What is the result of modifying the amino acid sequence of human insulin?

Insulins with different pharmacokinetic properties Signup and view all the answers

What is the availability of animal insulin in the United States?

Not available Signup and view all the answers

What is the primary purpose of a sliding scale insulin regimen?

To approximate daily insulin requirements based on pre-defined blood glucose ranges Signup and view all the answers

What does the basal insulin dose not change with in a sliding scale insulin regimen?

Blood glucose levels Signup and view all the answers

What is the limitation of sliding scale insulin therapy in covering a pre-meal high blood sugar?

The high blood sugar correction and food bolus can't be split Signup and view all the answers

What is the ratio of insulin to carb in a 1:10 insulin to carb ratio?

1 unit of insulin covers 10-15 gm of carbs Signup and view all the answers

What is the total daily insulin requirement for a person weighing 160 lbs according to the formula?

40 units/day Signup and view all the answers

What is the target blood sugar level for type I DM as per ADA?

154 mg/dl or less Signup and view all the answers

What is the disadvantage of sliding scale insulin therapy in terms of snacks and physical activity?

It can't cover insulin needs related to snacks or stress Signup and view all the answers

What is the biological equivalent of 1 IU of insulin?

34.7 ug of pure crystalline insulin Signup and view all the answers

Study Notes

Insulin and Glucose Lowering Agents

The pancreas produces peptide hormones: insulin, glucagon, and somatostatin, which play a crucial role in regulating metabolic activities, particularly glucose homeostasis.
Insulin is a small protein containing 51 amino acids arranged in two chains (A and B) linked by disulfide bridges.
Proinsulin is processed within the Golgi apparatus of beta cells and packaged into granules, where it is hydrolyzed into insulin and a residual connecting segment called C-peptide.
Insulin and C-peptide are secreted in equimolar amounts in response to all insulin secretagogues.

Mechanism of Insulin Release

Hyperglycemia results in increased intracellular ATP levels, which close ATP-dependent potassium channels, leading to depolarization of the beta cell and opening of voltage-gated calcium channels.
The resulting increased intracellular calcium triggers the secretion of insulin.

Insulin Secretion

Insulin is released from pancreatic beta cells at a low basal rate and at a much higher stimulated rate in response to various stimuli, including glucose, other sugars, amino acids, and hormones like glucagon-like polypeptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP).
Insulin secretion is also stimulated by high concentrations of fatty acids and β-adrenergic sympathetic activity.

Insulin Degradation

The liver and kidney are the two main organs that remove insulin from the circulation, with the liver clearing 60% of the insulin released from the pancreas and the kidney removing 35-40% of the endogenous hormone.
The half-life of circulating insulin is 3-5 minutes.

Insulin Receptor

Insulin receptors are found on the membranes of most tissues, and the biologic responses promoted by these insulin-receptor complexes have been identified in the primary target tissues regulating energy metabolism, including liver, muscle, and adipose tissue.

Effects of Insulin on Its Targets

Insulin promotes the storage of fat as well as glucose within specialized target cells and influences cell growth as well as the metabolic functions of a wide variety of tissues.

Diabetes Mellitus

Diabetes mellitus is a rapidly growing health problem that affects more than 350 million people worldwide, with elevated blood glucose associated with absent or inadequate pancreatic insulin secretion with or without impairment of insulin action.
The American Diabetes Association (ADA) recognizes four clinical classifications of diabetes: type 1, type 2, gestational diabetes mellitus, and other causes like genetic defects or medications.

Type 1 Diabetes

Type 1 diabetes is characterized by selective B cell destruction (severe or absolute insulin deficiency) and is further subdivided into immune-mediated (type 1a) and idiopathic (type 1b) forms.
Classical symptoms of type 1 diabetes include polydipsia, polyphagia, polyuria, and weight loss.
Type 1 diabetes requires exogenous insulin to treat hyperglycemia and life-threatening ketoacidosis.

Self-Monitoring of Blood Glucose

Capillary blood glucose measurements performed by patients themselves, as outpatients, are extremely useful in type 1 patients in whom "tight" metabolic control is attempted.
Continuous glucose monitoring (CGM) systems are also available for clinical use, utilizing a subcutaneous sensor that measures glucose concentrations in the interstitial fluid for 3-7 days.

Medications for Hyperglycemia

Human insulin is produced by recombinant DNA technology using strains of Escherichia coli or yeast that are genetically altered to contain the gene for human insulin.
Modification of the amino acid sequence of human insulin produces insulins with different pharmacokinetic properties.
Insulin preparations vary primarily in their onset and duration of activity.

Pharmacokinetics

Insulin is generally administered by subcutaneous injection, although an inhaled insulin formulation is also available.
Sliding scale insulin regimens approximate daily insulin requirements, depending on pre-defined blood glucose ranges for pre-meal or night time insulin dose.

Sliding Scale Insulin Therapy

Disadvantages of sliding scale therapy include:
- Not covering insulin needs related to snacks or stress and other activity
- Requiring carbohydrate counting
- Being less effective in covering a pre-meal high blood sugar
- Requiring a consistent diet and lifestyle
Sliding scale protocols (Bolus) involve calculating the dose of insulin based on the carbohydrate content of the meal and the blood glucose level.

Dose Calculation

The carbohydrate coverage dose is a bolus dose for food coverage, prescribed as an insulin-to-carb ratio.
The total daily insulin requirement can be calculated using formulas such as Total units daily = weight in pounds / 4 or Total units daily = weight in kg x 0.55.

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Description

Learn about the role of insulin and glucagon in regulating glucose homeostasis and metabolic activities in the body. This quiz covers the production and function of these peptide hormones.