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Details for messenger / hormone: insulin

EndoNet ID: ENH00096

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Synonyms

  • insulin
  • INS

General information

  • Insulin stimulates glucose uptake into muscle cells and fat and also inhibits glucagon expression and secretion from pancreatic alpha cells. [1]
  • The primary stimulus for insulin secretion is glucose, which must undergo metabolism in order for the secretion of insulin to occur. [2]
  • Peptide hormones.
  • Glucose-induced insulin secretio is modulated by other fuels as well as circulating and neural modulators to enhance the magnitude and rate of response of the beta cell. [2]
  • Disulfide-linked A- and B-chain processed from a common precursor.
  • insulin attenuates acetylcholine responses, which are mediated by endothelium-derived hyperpolarizing factor in small but not large arteries. [3]
  • A potent anabolic hormone and is essential for tissue development, growth and maintenance of glucose homeostasis. [4]
  • A major function of insulin is the acute regulation of glucose metabolism in muscle and fat cells via the InsR. [5]

Classification

Hormone function

  • metabolism
    • nutrient supply

    Chemical classification

    • hormone
      • genome-encoded
        • insulin family

      Composition

      A chain (1 times)

      Sequence
      GIVEQCCTS ICSLYQLEN YCN

      B chain (1 times)

      Sequence
      FVNQHLCGS HLVEALYLV CGERGFFYT 
      PKT

      Links to other resources

      UniProt P01308
      Ensembl ENSG00000129965
      KEGG hsa:3630
      • Anatomical structure: beta_cell_of_islet_of_Langerhans

        • syntaxin 4 also plays a role in glucose stimulated insulin secretion and that this process may be negatively regulated by the syntaxin 4-interacting protein Synip. [6]

        Influenced by:

        • gastric inhibitory polypeptide receptor
          in beta_cell_of_islet_of_Langerhans
          • siRNA-mediated knockdown of insulin receptor promoted enhanced glucagon secretion and complemented our in vivo findings [7]
          • intraislet insulin signaling plays a significant role in the regulation of alpha cell function [7]
          • insulin binding decreases the glucagon secretion [7]
          • The hormone glucose-dependent insulinotropic polypeptide (GIP) is an important regulator of insulin secretion. GIP has been shown to increase adenylyl cyclase activity, elevate intracellular Ca2+ levels, and stimulate a mitogen-activated protein kinase pathway in the pancreatic b-cell. [8]
          • Stimulation of GIP-mediated AA production was shown to be mediated via a Ca2+-independent phospholipase A2. Arachidonic acid is therefore a new component of GIP-mediated signal transduction in the b-cell. [8]
        • GLP-1R
          in beta_cell_of_islet_of_Langerhans
          • GLP-1 as attractive therapeutic approach for treatment of type 2 diabetes. [9]
          • GLP-1 induces glucose-dependent insulin secretion from pancreas and thereby acts to lower plasma glucose concentration without risk of hypoglycemia. [9]
        • alpha-2C adrenoreceptor
          in beta_cell_of_islet_of_Langerhans
          • A third mechanism for adrenaline-induced glucose elevation is inhibition of insulin release from the beta-cell mediated by alpha2-adrenoceptors. [10]
        • adrenomedullin receptor
          in beta_cell_of_islet_of_Langerhans
        • sst1
          in beta_cell_of_islet_of_Langerhans
          • Subtype-selective SSTR expression in islet cells could be the basis for preferential insulin suppression by SSTR1-specific ligands. [11]
        • sst2
          in beta_cell_of_islet_of_Langerhans
        • sst3
          in beta_cell_of_islet_of_Langerhans
        • sst5
          in beta_cell_of_islet_of_Langerhans
        • sst4
          in beta_cell_of_islet_of_Langerhans
        • integrin alpha-1/beta-1
          in beta_cell_of_islet_of_Langerhans
          • The interaction of alpha1beta1 with Col-IV also resulted in significant insulin secretion at basal glucose concentrations. [12]
        • insulin receptor
          in beta_cell_of_islet_of_Langerhans
          • Visfatin can significantly regulate insulin secretion, insulin receptor phosphorylation and intracellular signalling [13]
          • Glucose stimulation of β cells in culture has been shown to result in the activation of the IR as does the application of exogenous insulin, suggesting that insulin secreted from β cells binds to its receptor eliciting a physiological response [14]
        • CaSR
          in beta_cell_of_islet_of_Langerhans
          • The extracellular, G protein-linked Ca21-sensing receptor (CaSR), first identified in the parathyroid gland, is expressed in several tissues and cells and can be activated by Ca21 and some other inorganic cations and organic polycations; and stimulate insulin secretion in beta-cells. [15]
        • PACAP-R-1
          in pancreas
          • The signaling phenotype of PACAPR TM4 (Pituitary adenylate cyclase-activating polypeptide transmembrane domain IV) is characteristic of the PACAP receptor involved in regulation of insulin secretion from pancreatic β islets, a tissue expressing transcripts for PACAPR TM4 but not for PACAPR or its longer splice variant forms. These findings are consistent with a role of PACAPR TM4 in the physiological control of insulin release by PACAP in β-islet cells. [16]
        • EP3
          in beta_cell_of_islet_of_Langerhans
          • EP3 is the Prostaglandin E2 receptor subtype whose post-receptor effect is to decrease adenylyl cyclase activity and, thereby, insulin secretion. [17]
        • beta-3 adrenoreceptor
          in beta_cell_of_islet_of_Langerhans
          • Human Beta3-AR produced an increased baseline and ligand-dependent insulin secretion. [18]
          • Cells express the Beta3-AR, and its activation contributes to the regulation of insulin secretion. [18]
        • free fatty acid receptor 1
          in beta_cell_of_islet_of_Langerhans
          • Recent studies documented that free fatty acid receptor 1 (GPR40) mediates both acute stimulatory and chronic inhibitory effects of FFAs on insulin secretion and that GPR40 signaling is linked to impaired glucose homeostasis. [19]
        • free fatty acid receptor 1
          in beta_cell_of_islet_of_Langerhans
          • Recent studies documented that free fatty acid receptor 1 (GPR40) mediates both acute stimulatory and chronic inhibitory effects of FFAs on insulin secretion and that GPR40 signaling is linked to impaired glucose homeostasis. [19]
        • VDR
          in beta_cell_of_islet_of_Langerhans
          • Insulin but not glucagon release is reduced after stimulation with glucose and arginine in isolated perfused pancreas from vitamin D-deficient rats. [20]
          • Glucose tolerance and insulin secretion are impaired in vitamin D-deficient rats in vivo. [21]
          • nonfunctioning VDR is assiciated with impaired glucose tolerance and reduced maximum insulin secretory capacity, independent of changes in calcium homeostasis. [22]
        • PPAR-alpha
          in beta_cell_of_islet_of_Langerhans
          • Acute activation of PPAR-alpha, but not PPAR-gamma, has the potential to stimulate mitochondrial ß-oxidation and potentiate glucose-stimulated insulin secretion (GSIS) in both INS-1E insulinoma cells and rat islets. Thus, regulation of PPAR-alpha expression and activity appears essential for adjusting ß-cells to metabolic challenges and for maintenance of ß-cell function. [23]
        • CRF-R2
          in ventromedial_nucleus_of_hypothalamus
          • The VMH is a brain region seemingly involved in the modulation of insulin secretion as ablation of the VMH led to increase in the parasympathetic tone to the pancreas and insulin oversecretion. [24]
          • There is evidence that the CRF-R2 in the VMH mediates the anorectic effects of CRF. [25]
          • A part of insulin central effects may be mediated through its regulation of CRF-R2 VMH expression. [26]
        • leptin receptor
          in adipose_tissue
          • Leptin has an important physiological role an inhibitor of insulin secretion and the failure of leptin to inhibit insulin secretion from the beta-cells may explain, in part, the development of hyperinsulinemia, insulin resistance, and the progression to non-insulin-dependent diabetes mellitus. [27]
        • leptin receptor
          in pancreas
          • Functional leptin receptor is present in pancreatic islets and suggest that leptin overproduction, particularly from abdominal adipose tissue, may modify directly both basal and glucose-stimulated insulin secretion. [28]
        • TNFR1
          in adipose_tissue
          • TNF alpha regulates leptin release from adipocztes, therebz influencing insulin secretion. [29]
          • The ability of leptin and TNF/alpha to suppress insulin secretion from the pancreas beta cells might also contribute to the abnormalities in glucose homeostasis in obesity. [29]
        • PRLR
          in pancreas
          • PRL is known to have direct effects on pancreatic function, increasing insulin secretion and decreasing glucose threshold for insulin secretion. [30]
        • beta-2 adrenoreceptor
          in beta_cell_of_islet_of_Langerhans
          • The hypoglycaemia unawareness in patients with insulin dependent diabetes mellitus was associated with dysfunction of the proximal beta2-adrenergic signal pathway. [31]
      • Anatomical structure: arcuate_nucleus_of_hypothalamus

        Influenced by:

        • insulin receptor
          in arcuate_nucleus_of_hypothalamus
          • insulin stimulates phosphorylation of signalling proteins in ARC [32]
      • Anatomical structure: fat_cell_of_white_fat

        Influenced by:

        • beta-3 adrenoreceptor
          in fat_cell
          • b3-Adrenergic receptors (b3-ARs) are expressed predominantly on white and brown adipocytes, and acute treatment of mice with CL 316,243, a potent and highly selective b3-AR agonist, produces a 2-fold increase in energy expenditure, a 50–100-fold increase in insulin levels, and a 40–50% reduction in food intake. [33]
          • CL-mediated effects on insulin levels and food intake and only minimally restored effects on oxygen consumption, indicating that any effect on insulin secretion and food intake, and a full stimulation of oxygen consumption required the presence of b3-ARs in white adipocytes. [33]

      Targets

      CellIGF-1RInsR-Binsulin receptorinsulin receptor isoform short
      acidophil somatotroph cell of anterior pituitary Present
      Phenotypes
      • cell growth
      • positive regulation of cell proliferation
      • negative regulation of apoptosis
      • transformation
      Influences
      • GH
      adrenal cortex Present
      alpha cell of islet of Langerhans Present
      Influences
      • glucagon
      arcuate nucleus of hypothalamus Present
      Influences
      • NPY
      • AGRP
      • alpha-MSH
      • insulin
      basophil corticotroph cell of anterior pituitary Present
      Phenotypes
      • tertiary adrenal insufficiency
      Influences
      • ACTH
      • lipotropin beta
      beta cell of islet of Langerhans Present
      Phenotypes
      • Diabetes mellitus type 2
      • Leprechaunism
      • Diabetes mellitus type 1
      • Maturity onset diabetes of the young
      • Insulimona
      • Hypoglycemia
      Influences
      • insulin receptor substrate 1
      • insulin
      chondrocyte Present
      continuous vascular endothelial cell of blood vessels and lymphatics Present
      continuous vascular endothelial cell of blood vessels and lymphatics Present
      Influences
      • annexin A2
      Present
      Influences
      • annexin A2
      • NO
      fat cell Present
      Influences
      • VEGF-165
      • IL-8
      • leptin
      heart Present
      lung Present
      Influences
      • amphiregulin
      microvascularendothelial cell Present
      osteoblast Present
      skeleton muscle Present
      Reference