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Details for anatomical structure: beta cell of islet of Langerhans

EndoNet ID: ENC00174

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Synonyms

beta cell of islet of Langerhans, b-cell of islet of Langerhans, Endocrinocytus beta

General information

secreting insulin; insulin is responsible for lowering the blood sugar level and stimulates growth

Links to other resources

Cytomer cy0011208

Larger structures

    Substructures

      Secreted hormones

      • Hormone: urocortin-3

      • Hormone: IAPP

        • Amylin is colocated with insulin in the pancreatic beta cells and is cosecreted with insulin from the pancreatic beta cells in a constant molar ratio. The ratio of insulin to amylin is approximately 20 to 1. [1]
        • In persons without diabetes amylin is rapidly increased after meal. In type 1 diabetes, amylin, like insulin, is virtually absent. In insulin-treated type 2 diabetes amylin and insulin are still produced but in amounts insufficient to maintain normal glucose levels. [1]
      • Hormone: FAM3B-a

        • Pancreatic-derived factor (PANDER, FAM3B) is a pancreatic islet-specific cytokine-like protein that is secreted from β-cells upon glucose stimulation. [2]
      • Hormone: IGF-2

        • Co-localization of IGF-2 in B-cells was determined by immunocytochemistry. S.456 [3]
      • Hormone: insulin

        • 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. [4]

        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 [5]
          • intraislet insulin signaling plays a significant role in the regulation of alpha cell function [5]
          • insulin binding decreases the glucagon secretion [5]
          • 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. [6]
          • 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. [6]
        • GLP-1R
          in beta_cell_of_islet_of_Langerhans
          • GLP-1 as attractive therapeutic approach for treatment of type 2 diabetes. [7]
          • GLP-1 induces glucose-dependent insulin secretion from pancreas and thereby acts to lower plasma glucose concentration without risk of hypoglycemia. [7]
        • 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. [8]
        • 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. [9]
        • 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. [10]
        • insulin receptor
          in beta_cell_of_islet_of_Langerhans
          • Visfatin can significantly regulate insulin secretion, insulin receptor phosphorylation and intracellular signalling [11]
          • 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 [12]
        • 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. [13]
        • 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. [14]
        • 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. [15]
        • beta-3 adrenoreceptor
          in beta_cell_of_islet_of_Langerhans
          • Human Beta3-AR produced an increased baseline and ligand-dependent insulin secretion. [16]
          • Cells express the Beta3-AR, and its activation contributes to the regulation of insulin secretion. [16]
        • 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. [17]
        • 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. [17]
        • 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. [18]
          • Glucose tolerance and insulin secretion are impaired in vitamin D-deficient rats in vivo. [19]
          • nonfunctioning VDR is assiciated with impaired glucose tolerance and reduced maximum insulin secretory capacity, independent of changes in calcium homeostasis. [20]
        • 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. [21]
        • 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. [22]
          • There is evidence that the CRF-R2 in the VMH mediates the anorectic effects of CRF. [23]
          • A part of insulin central effects may be mediated through its regulation of CRF-R2 VMH expression. [24]
        • 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. [25]
        • 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. [26]
        • TNFR1
          in adipose_tissue
          • TNF alpha regulates leptin release from adipocztes, therebz influencing insulin secretion. [27]
          • 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. [27]
        • PRLR
          in pancreas
          • PRL is known to have direct effects on pancreatic function, increasing insulin secretion and decreasing glucose threshold for insulin secretion. [28]
        • 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. [29]
      • Hormone: insulin receptor substrate 1

        Influenced by:

        • insulin receptor
          in beta_cell_of_islet_of_Langerhans
          • There might be a direct link between the insulin receptor signaling pathway and the Ca2+ -dependent pathways regulating insulin secretion of b-cells. During regulated insulin secretion, released insulin binds the b-cell insulin receptor and activates IRS-1, thus further increasing cytosolic Ca2+ by reducing Ca2+ uptake. [30]

      Receptors

      • Receptor: Putative tumor suppressor protein EXTL3

        • EXTL3 was identified as the Reg-1α receptor involved in the regulation of pancreatic β-cells for maintaining the β-cell mass [31]

        Induced phenotype:

        • regeneration of beta-cells of pancreas
          • A Reg receptor, EXTL3, mediates the Reg growth signal for β-cell regeneration. [31]
      • Receptor: gastric inhibitory polypeptide receptor

        Influences:

        • insulin
          • siRNA-mediated knockdown of insulin receptor promoted enhanced glucagon secretion and complemented our in vivo findings [5]
          • intraislet insulin signaling plays a significant role in the regulation of alpha cell function [5]
          • insulin binding decreases the glucagon secretion [5]
          • 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. [6]
          • 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. [6]
      • Receptor: GLP-1R

        • The GLP-1 receptor is expressed in beta cells of the islet of Langerhans [32]
        • The GLP-1 receptor is strongly expressed on the surface of the β cells facing the endothelium. [33]

        Induced phenotype:

        • regulation of glucose homeostasis
          • Upon secretion, GLP-1 acts on a small selection of tissues to regulate glucose homeostasis. [34]
          • When administered to type 2 diabetic subjects, GLP-1 normalizes blood glucose levels, increases circulating insulin, and diminishes glucagon secretion. [35]
        • positive regulation of anti-apoptosis
          • The action of GLP-1 on cell proliferation is complemented by its effect on cell survival. Indeed, GLP-1 and its analogs exhibited anti-apoptotic properties in several rodent models. [34]
          • Mice with disruption of the Glp1r gene exhibit enhanced β-cell death and more severe hyperglycaemia following administration of the β-cell toxin, steptozotocin . [36]
        • pancreatc B cell differentiation
          • The biologic actions of GLP-1 in the β-cell include restoration of glucose competence in glucose-resistant β-cells. [37]
          • The biologic actions of GLP-1 in the β-cell include stimulation of β-cell mass expansion. [34]
          • GLP-1 acts as a growth factor for the β-cell both in experimental animal models and cultured β-cells by stimulating proliferation, survival and differentiation. [34]
          • GLP-1 has been initially shown to promote β-cell replication in vitro as well as in vivo in a partial pancreatectomy rat model of type 2 diabetes. [38]
        • inhibition of gastric emptying

        Influences:

        • insulin
          • GLP-1 as attractive therapeutic approach for treatment of type 2 diabetes. [7]
          • GLP-1 induces glucose-dependent insulin secretion from pancreas and thereby acts to lower plasma glucose concentration without risk of hypoglycemia. [7]
      • Receptor: alpha-2C adrenoreceptor

        Influences:

        • insulin
          • A third mechanism for adrenaline-induced glucose elevation is inhibition of insulin release from the beta-cell mediated by alpha2-adrenoceptors. [8]
      • Receptor: beta-2 adrenoreceptor

        Influences:

        • insulin
          • The hypoglycaemia unawareness in patients with insulin dependent diabetes mellitus was associated with dysfunction of the proximal beta2-adrenergic signal pathway. [29]
      • Receptor: sst1

        Influences:

        • insulin
          • Subtype-selective SSTR expression in islet cells could be the basis for preferential insulin suppression by SSTR1-specific ligands. [9]
      • Receptor: adrenomedullin receptor

        Influences:

        • insulin
      • Receptor: sst2

        Influences:

        • insulin
      • Receptor: sst5

        Influences:

        • insulin
      • Receptor: sst3

        Influences:

        • insulin
      • Receptor: sst4

        Influences:

        • insulin
      • Receptor: LRP5

      • Receptor: integrin alpha-1/beta-1

        Influences:

        • insulin
          • The interaction of alpha1beta1 with Col-IV also resulted in significant insulin secretion at basal glucose concentrations. [10]
      • Receptor: insulin receptor

        Induced phenotype:

        • Diabetes mellitus type 2
          • Diabetes is a metabolic disorder, the primary manifestation of which is elevated circulating blood glucose levels. [39]
          • Mutations in the insulin receptor can lead to severe insulin resistance. [40]
          • Insulin resistance can occur due to downregulation of insulin receptors. [41]
        • Leprechaunism
          • Mutations in the insulin receptor (null phenotype) can lead to severe insulin resistance and clinical defects such as leprechaunism. [40]
        • Diabetes mellitus type 1
          • Type 1 diabetes (also called juvenile-onset diabetes mellitus and insulin-dependent diabetes mellitus) is caused by an absolute insulin deficiency, the result of a loss of the insulin-producing beta cells of the pancreas. [42]
        • Maturity onset diabetes of the young
          • Factors that affect insulin sensitivity, such as infection, puberty, pregnancy, and (in rare cases) obesity, may trigger the onset of diabetes and increase the severity of hyperglycemia in patients with MODY [43]
        • Insulimona
          • Insulinoma is the most common cause of endogenous hyperinsulinemic hypoglycemia in adults. It is a benign tumor of the pancreatic beta cells. Insulinoma secretes excess insulin resulting in hypoglycemia. [44]
        • Hypoglycemia
          • Endogenous hyperinsulinemic hypoglycemia in adults is amongst others caused by excessive insulin. [44]

        Influences:

        • insulin receptor substrate 1
          • There might be a direct link between the insulin receptor signaling pathway and the Ca2+ -dependent pathways regulating insulin secretion of b-cells. During regulated insulin secretion, released insulin binds the b-cell insulin receptor and activates IRS-1, thus further increasing cytosolic Ca2+ by reducing Ca2+ uptake. [30]
        • insulin
          • Visfatin can significantly regulate insulin secretion, insulin receptor phosphorylation and intracellular signalling [11]
          • 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 [12]
      • Receptor: CaSR

        Influences:

        • insulin
          • 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. [13]
      • Receptor: EP3

        Influences:

        • insulin
          • EP3 is the Prostaglandin E2 receptor subtype whose post-receptor effect is to decrease adenylyl cyclase activity and, thereby, insulin secretion. [15]
      • Receptor: beta-3 adrenoreceptor

        Influences:

        • insulin
          • Human Beta3-AR produced an increased baseline and ligand-dependent insulin secretion. [16]
          • Cells express the Beta3-AR, and its activation contributes to the regulation of insulin secretion. [16]
      • Receptor: free fatty acid receptor 1

        Influences:

        • insulin
          • 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. [17]
        • insulin
          • 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. [17]
      • Receptor: VDR

        Influences:

        • insulin
          • Insulin but not glucagon release is reduced after stimulation with glucose and arginine in isolated perfused pancreas from vitamin D-deficient rats. [18]
          • Glucose tolerance and insulin secretion are impaired in vitamin D-deficient rats in vivo. [19]
          • nonfunctioning VDR is assiciated with impaired glucose tolerance and reduced maximum insulin secretory capacity, independent of changes in calcium homeostasis. [20]
      • Receptor: PPAR-alpha

        Influences:

        • insulin
          • 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. [21]
      Reference