Insulin

8 Key excerpts on "Insulin"

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  eBook - ePub

  Metabolic Risk for Cardiovascular Disease

  • Robert H. Eckel(Author)
  • 2011(Publication Date)
  • Wiley-Blackwell

    (Publisher)

  Chapter 1 Insulin action and beta-cell function: role in metabolic regulation Kristina M. Utzschneider and Steven E. Kahn Regulation of fuel utilization in health and disease

  The normal processing and utilization of fuels is tightly regulated by hormonal, neural, and intracellular mechanisms so that carbohydrates, proteins, and fats supply energy to the brain, muscles, and other tissues, and excess fuel is stored efficiently for use during periods of fasting or increased energy needs. Two key players in the balance of hormones regulating these processes are Insulin and glucagon.

  Insulin is secreted by the islet beta-cell in response to glucose, amino acids, peptides, and fatty acids and then promotes tissue uptake of glucose and glyco-gen synthesis. Insulin also acts on lipid metabolism by promoting enzymes involved in de novo lipogenesis, while suppressing those enzymes involved in lipid oxidation and lipolysis, resulting in a decrease in circulating free fatty acids (FFAs). The net result is a shift towards utilization of glucose as the primary fuel. Insulin’s effects are mainly anabolic as Insulin levels increase when nutrient availability is high. During times when Insulin levels are low, such as during fasting, these processes reverse and fuel selection shifts to preferentially utilize fat. Insulin also acts centrally in the hypothalamus as a satiety signal by interacting with neural centers that regulate food intake.

  In contrast to Insulin, the hormone glucagon, which is secreted by the islet alpha-cell, acts as a catabolic hormone, stimulating production of glucose via glycogenolysis and gluconeogenesis, primarily in response to hypoglycemia. Glucagon is also important in the regulation of basal and postprandial glucose levels, with the balance of this hormone with Insulin being important. Thus, when Insulin levels rise, as occurs after nutrient ingestion, glucagon levels will normally decrease.

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  eBook - ePub

  Hormones

  • Anthony W. Norman, Gerald Litwack(Authors)
  • 1997(Publication Date)
  • Academic Press

    (Publisher)

  These can include (1) the intestinal absorption and concomitant systemic transport to storage depots (liver, muscle, and/or adipose tissue) of foodstuffs (e.g., carbohydrates, proteins, fat); (2) muscular activity; (3) thermogenesis and response to environmental extremes of heat and cold; (4) starvation; (5) pregnancy/lactation; and (6) disease or injury states. The endocrine gland largely responsible for the maintenance of blood glucose levels and the proper cellular uptake and exchange of “fuel metabolites” is the pancreas. The principal hormones secreted by the pancreas are Insulin and glucagon. In addition, the pancreas secretes a number of other peptide hormones (see Table 7-6). Table 7-6 Hormones and Proteins Secreted by the Pancreas a IAPP is structurally homologous to calcitonin gene-related peptide (CGRP); see Figure 9-4. b The chromogranins A, B, and C are a family of closely related acidic proteins that are produced by many neuroendocrine cells. Chromogranins A are produced by pancreatic α, β, and F cells of the pancreatic islet. c The B cells also secrete small quantities of procathepsin B, carboxypeptidase H, endopeptidases I and II, and peptidylglycan α- amidating monooxygenase. Insulin is a pluripotent hormone in that it has a wide sphere of influence; directly or indirectly it affects virtually every organ and tissue in the body. The main function of Insulin is to stimulate anabolic reactions for carbohydrates, proteins, and fats, all of which will have the metabolic consequence of producing a lowered blood glucose level. Glucagon can be thought of as an indirect antagonist of Insulin. Glucagon stimulates catabolic reactions that ultimately lead to an elevation in blood glucose levels

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  eBook - ePub

  Biopharmaceuticals

  Biochemistry and Biotechnology

  • Gary Walsh(Author)
  • 2013(Publication Date)
  • Wiley-Blackwell

    (Publisher)

  in vitro studies and at high Insulin concentrations. Some of these mitogenic effects are likely mediated via the Insulin-like growth factor 1 (1GF-1) receptor and their physiological relevance is questionable.

  Although many cells in the body express the Insulin receptor, its most important targets are skeletal muscle fibres, hepatocytes and adipocytes, where it often antagonizes the effects of glucagon (Table 8.1 ). The most potent known stimulus of pancreatic Insulin release is an increase in blood glucose levels, often occurring after meal times. Insulin orchestrates a suitable metabolic response to the absorption of glucose and other nutrients in a number of ways:

  Table 8.1. Some metabolic effects of Insulin. These effects are generally countered by other hormones (glucagon and, in some cases, adrenaline). Hence, the overall effect noted often reflects the relative rates of these hormones present in the plasma

  • it stimulates glucose transport (and transport of amino acids, K+ ions and other nutrients) into cells, thus reducing their blood concentration;
  • it stimulates (or helps to stimulate) intracellular biosynthetic (anabolic) pathways, such as glycogen synthesis (Table 8.1 ), which helps to convert the nutrients into a storage form in the cells;
  • it inhibits (or helps to inhibit) catabolic pathways, such as glycogenolysis;
  • it stimulates protein and DNA synthesis (which underlies Insulin’s growth-promoting activity).

  In general, Insulin achieves such metabolic control by inducing the dephosphorylation of several key regulatory enzymes in mainline catabolic or anabolic pathways. This inhibits the former and stimulates the latter pathway types. These effects are often opposed by other hormones, notably glucagon and adrenaline. Thus, when blood glucose concentrations decrease (e.g. during fasting), Insulin levels decrease and the (largely catabolic) effects of glucagon become more prominent. Insulin also induces its characteristic effects by altering the level of transcription of various genes, many of which code for metabolic enzymes. Another gene upregulated by Insulin is that of the integral membrane glucose transporter.

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  eBook - ePub

  The Endocrine System,E-Book

  • Joy P. Hinson Raven, Peter Raven, Shern L. Chew, Stephen H. Hughes(Authors)
  • 2022(Publication Date)
  • Elsevier

    (Publisher)

  Chapter 11: Insulin and the regulation of plasma glucose

  Chapter objectives

  After studying this chapter you should be able to:

  1. Explain how plasma glucose concentrations are maintained within a normal range.

  2. Explain the mechanisms controlling the secretion of Insulin.

  3. Describe the actions of Insulin.

  4. Explain the consequences of a deficiency in Insulin production or action.

  5. Describe the main treatment options for type 1 and type 2 diabetes mellitus.

  6. Describe the ‘metabolic syndrome’.

  Introduction

  The brain uses glucose, its main energy source, at a much faster rate than does any other tissue in the body (Fig. 11.1 ). It is perhaps surprising, therefore, that the brain does not keep significant stores of glucose. Instead, the brain relies on obtaining a constant supply of glucose from the blood. As a result, the brain is extremely sensitive to a fall in blood glucose levels. Meanwhile, a sustained high level of blood glucose causes problems due to the increased osmolarity of blood; ultimately, this leads to tissue damage as a result of inappropriate glycosylation in body tissues. Circulating concentrations of glucose are therefore maintained within relatively tight limits. This requires a complex system of control because the plasma glucose levels can rise rapidly after a meal, but could also become very low during periods of fasting.

  There are several hormones that act to increase the circulating glucose concentrations, but the major hormone involved in lowering the blood glucose load is Insulin, a hormone secreted by the pancreas. A deficiency of either Insulin production or effectiveness results in a condition known as diabetes mellitus. There are two principal forms of this disorder: type 1, which is Insulin-dependent (IDDM) and results from loss of Insulin production; and type 2 or ‘non-Insulin-dependent’ (NIDDM), which is a condition of Insulin resistance (Table 11.1 ).

  Fig. 11.1

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  eBook - ePub

  Diabetes

  Clinician's Desk Reference

  • M. Cecilia Lansang, Richard David Leslie, Tahseen A. Chowdhury, Keren Zhou(Authors)
  • 2022(Publication Date)
  • CRC Press

    (Publisher)
• Overactivity of glucose-6-phosphatase contributes to the increased and relatively Insulin-insensitive hepatic glucose production in type 2 diabetes.
• Metformin and the thiazolidinediones (see Chapter 14 ) appear to reduce the activity of this enzyme, although it is not clear whether their effects are direct or mediated through some other upstream action.

The role and regulation of Insulin

• Insulin is the predominant hormone regulating blood glucose concentration. It is the key hormone involved in both the storage and the controlled release of energy.
• Diabetes occurs as a result of a failure of Insulin production and secretion (Insulin deficiency) and/or the loss of response to Insulin (Insulin resistance).
• Insulin is coded for by genes on chromosome 11 and is synthesized and secreted by the β cells of the islets of Langerhans in the pancreas. Complex cellular events trigger the release of Insulin from the secretory granules of these cells.

Hormones called incretins are peptides secreted by the gut in response to a meal and stimulate the secretion of Insulin. Of these, glucagon-like peptide-1 (GLP-1, produced by the lower intestine) and glucose-dependent Insulinotropic polypeptide (GIP, produced by the upper intestine) are the better-studied incretins.

• After secretion, Insulin enters the portal circulation, which takes it to the liver, a prime target organ of Insulin action.
• Although Insulin is the major regulator of intermediary metabolism, its actions are modified by other hormones, e.g. glucagon, epinephrine (adrenalin), cortisol, and growth hormone. Such counter-regulatory hormones increase glucose production from the liver and, for a given level of Insulin, reduce utilization of glucose in adipose tissue and muscle.