Assessment of human pancreatic islet architecture and composition by laser scanning confocal microscopy. J Histochem Cytochem ; 53 : — Roles of pancreatic polypeptide in regulation of food intake. Peptides ; 23 : — The ghrelin cell: a novel developmentally regulated islet cell in the human pancreas. Regul Pept ; : 63— Islet cell function: alpha and beta cells—partners towards normoglycaemia.
Int J Clin Pract Suppl ; : 2—7. Somatostatin secreted by islet delta-cells fulfills multiple roles as a paracrine regulator of islet function. Diabetes ; 58 : — Pancreatic polypeptide reduces appetite and food intake in humans.
J Clin Endocrinol Metab ; 88 : — The unique cytoarchitecture of human pancreatic islets has implications for islet cell function. Effect of intranasal glucagon on blood glucose levels in healthy subjects and hypoglycaemic patients with insulin-dependent diabetes.
Lancet ; 1 : — Glucose-stimulated insulin secretion: a newer perspective. J Diabetes Investig ; 4 : — Insulin regulation of glucose uptake: a complex interplay of intracellular signalling pathways. Diabetologia ; 45 : — J Biol Chem ; : — Targeted disruption of the glucose transporter 4 selectively in muscle causes insulin resistance and glucose intolerance. Nat Med ; 6 : — Rapid action of insulin and cyclic AMP in the regulation of functional messenger RNA coding for glucokinase in rat liver.
SREBP-1c mediates the insulin-dependent hepatic glucokinase expression. Diabetologia ; 49 : — Reciprocal regulation of glycogen phosphorylase and glycogen synthase by insulin involving phosphatidylinositol-3 kinase and protein phosphatase-1 in HepG2 cells. Mol Cell Biochem ; : — Mechanism of control of hepatic glycogenesis by insulin. Studies on the effects of insulin and acetylcholine on activation of glycogen synthase and on glycogenesis in hepatocytes.
Biochem Biophys Res Commun ; 61 : — The sequential inactivation of glycogen phosphorylase and activation of glycogen synthetase in liver after the administration of glucose to mice and rats. The mechanism of the hepatic threshold to glucose. Eur J Biochem ; 41 : — Identification of a sequence in the PEPCK gene that mediates a negative effect of insulin on transcription.
Science ; : — A multicomponent insulin response sequence mediates a strong repression of mouse glucosephosphatase gene transcription by insulin. Insulin inhibits hepatocellular glucose production by utilizing liver-enriched transcriptional inhibitory protein to disrupt the association of CREB-binding protein and RNA polymerase II with the phosphoenolpyruvate carboxykinase gene promoter.
The forkhead transcription factor Foxo1 Fkhr confers insulin sensitivity onto glucosephosphatase expression. J Clin Invest ; : — Regulation of glucosephosphatase gene expression by protein kinase Balpha and the forkhead transcription factor FKHR. Evidence for insulin response unit-dependent and -independent effects of insulin on promoter activity.
Inhibition of GSK-3 selectively reduces glucosephosphatase and phosphatase and phosphoenolypyruvate carboxykinase gene expression. Diabetes ; 50 : — Stimulation of lipogenesis by insulin in swine adipose tissue: antagonism by porcine growth hormone. J Anim Sci ; 62 : — Insulin and rosiglitazone regulation of lipolysis and lipogenesis in human adipose tissue in vitro.
Diabetes ; 51 : — Physiologic hyperinsulinemia stimulates protein synthesis and enhances transport of selected amino acids in human skeletal muscle. J Clin Invest ; 95 : — Stimulus-secretion coupling in pancreatic beta cells.
J Cell Biochem ; 55 Suppl : 54— Triggering and amplifying pathways of regulation of insulin secretion by glucose. Diabetes ; 49 : — The plasma insulin response to glucose infusion in healthy subjects and in diabetes mellitus.
Acta Endocrinol Copenh ; 55 : — Insulin responses to glucose: evidence for a two pool system in man. J Clin Invest ; 48 : — Dynamics of insulin secretion by the perfused rat pancreas. Endocrinology ; 83 : — Regulation of two insulin granule populations within the reserve pool by distinct calcium sources.
J Cell Sci ; Pt 24 : — Fast insulin secretion reflects exocytosis of docked granules in mouse pancreatic B-cells. Pflugers Arch ; : 43— Structural changes are associated with soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor complex formation. Munc promotes large dense-core vesicle docking. Neuron ; 31 : — Munc18b is a major mediator of insulin exocytosis in rat pancreatic beta-cells.
Diabetes ; 62 : — Biochemistry ; 37 : — Endocr Rev ; 28 : — EMBO J ; 14 : — Syntaxin-3 regulates newcomer insulin granule exocytosis and compound fusion in pancreatic beta cells. Diabetologia ; 56 : — Dual role of VAMP8 in regulating insulin exocytosis and islet beta cell growth.
Cell Metab ; 16 : — Calcium-sensing beyond neurotransmitters: functions of synaptotagmins in neuroendocrine and endocrine secretion. Biosci Rep ; 29 : — Expression and localisation of synaptotagmin isoforms in endocrine beta-cells: their function in insulin exocytosis. J Cell Sci ; Pt 9 : — J Physiol ; Pt 6 : — Localization and functional role of synaptotagmin III in insulin secretory vesicles in pancreatic beta-cells.
Diabetes ; 46 : — J Cell Sci ; Pt 15 : — Physiological roles for G protein-regulated adenylyl cyclase isoforms: insights from knockout and overexpression studies. Neurosignals ; 17 : 5— Epac2-dependent rap1 activation and the control of islet insulin secretion by glucagon-like peptide Vitam Horm ; 84 : — J Physiol ; Pt 24 : — EMBO J ; 18 : — J Gen Physiol ; 94 : — Pflugers Arch ; : — L-type calcium channels in insulin-secreting cells: biochemical characterization and phosphorylation in RINm5F cells.
Mol Endocrinol ; 11 : — J Gen Physiol ; : — Protein kinase A-dependent and -independent stimulation of exocytosis by cAMP in mouse pancreatic B-cells. J Physiol ; Pt 1 : — Glucose sensing in L cells: a primary cell study. Cell Metab ; 8 : — Nutrient-dependent secretion of glucose-dependent insulinotropic polypeptide from primary murine K cells.
Diabetologia ; 52 : — Glucagon-like peptide-1 amide and glucose-dependent insulinotropic polypeptide secretion in response to nutrient ingestion in man: acute post-prandial and h secretion patterns.
J Endocrinol ; : — Glutamine potently stimulates glucagon-like peptide-1 secretion from GLUTag cells. Diabetologia ; 47 : — Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes ; 61 : — Free fatty acids regulate gut incretin glucagon-like peptide-1 secretion through GPR Nat Med ; 11 : 90— Gastric inhibitory polypeptide: effect on glucose-induced insulin release from isolated rat pancreatic islets in vitro.
Diabetologia ; 11 : — Stimulation of insulin secretion by gastric inhibitory polypeptide in man. J Clin Endocrinol Metab ; 37 : — Glucagon-like peptide-1 a physiological incretin in man. Lancet ; 2 : — Expression and functional activity of glucagon, glucagon-like peptide I, and glucose-dependent insulinotropic peptide receptors in rat pancreatic islet cells. Diabetes ; 45 : — Glucagon-like peptide I stimulates insulin gene expression and increases cyclic AMP levels in a rat islet cell line.
Functional expression of the rat pancreatic islet glucose-dependent insulinotropic polypeptide receptor: ligand binding and intracellular signaling properties. Endocrinology ; : — Functional expression of the rat glucagon-like peptide-I receptor, evidence for coupling to both adenylyl cyclase and phospholipase-C. Endocrinology ; : 57— Molecular cloning, functional expression, and signal transduction of the GIP-receptor cloned from a human insulinoma.
FEBS Lett ; : 23— Glucagon-like peptide I increases cytoplasmic calcium in insulin-secreting beta TC3-cells by enhancement of intracellular calcium mobilization. Diabetes ; 44 : — The role of the free cytosolic calcium level in beta-cell signal transduction by gastric inhibitory polypeptide and glucagon-like peptide I Endocrinology ; : 94— Mol Cell Endocrinol ; 96 : 85— Cell Calcium ; 15 : — Cloning and functional expression of the human islet GLP-1 receptor. Demonstration that exendin-4 is an agonist and exendin- an antagonist of the receptor.
Diabetes ; 42 : — Snapin mediates incretin action and augments glucose-dependent insulin secretion. Cell Metab ; 13 : — Synaptotagmin-7 phosphorylation mediates GLPdependent potentiation of insulin secretion from beta-cells.
Biochem Biophys Res Commun ; : 97— Cell Tissue Res ; : — Free fatty acids regulate insulin secretion from pancreatic beta cells through GPR Nature ; : — Propionate inhibits glucose-induced insulin secretion in isolated rat pancreatic islets. Cell Biochem Funct ; 25 : — Inhibition of insulin release by norepinephrine in man. Inhibition of insulin secretion via distinct signaling pathways in alpha2-adrenoceptor knockout mice. Eur J Endocrinol ; : — A receptor mechanism for the inhibition of insulin release by epinephrine in man.
J Clin Invest ; 46 : 86— Parasympathetic innervation and function of endocrine pancreas requires the glial cell line-derived factor family receptor alpha2 GFRalpha2.
Diabetes ; 54 : — Effects of hypothalamic lesion on pancreatic autonomic nerve activity in the rat. Brain Res ; : — Sympathetic innervation during development is necessary for pancreatic islet architecture and functional maturation. Cell Rep ; 4 : — Insulin receptors are widely distributed in human brain and bind human and porcine insulin with equal affinity.
Diabet Med ; 14 : — Insulin receptor expression and activity in the brains of nondiabetic sporadic Alzheimer's disease cases. Int J Alzheimers Dis ; : Autoradiographic localization of insulin receptors in rat brain: prominence in olfactory and limbic areas. Neuroscience ; 17 : — Localization of insulin receptor mRNA in rat brain by in situ hybridization. Decreasing hypothalamic insulin receptors causes hyperphagia and insulin resistance in rats. Nat Neurosci ; 5 : — Periventricular hypothalamic cells in the rat brain contain insulin mRNA.
Neuropeptides ; 8 : 93— Leptin and insulin stimulation of signalling pathways in arcuate nucleus neurones: PI3K dependent actin reorganization and KATP channel activation. BMC Neurosci ; 5 : The regulation of glucose-excited neurons in the hypothalamic arcuate nucleus by glucose and feeding-relevant peptides.
Diabetes ; 53 : — Acute hyperinsulinemia and its reversal by vagotomy after lesions of the ventromedial hypothalamus in anesthetized rats. Consequences of ventromedial hypothalamic lesions upon insulin and glucagon secretion by subsequently isolated perfused pancreases in the rat. J Clin Invest ; 65 : — Effect of ventromedial hypothalamic lesions on the secretion of somatostatin, insulin, and glucagon by the perfused rat pancreas.
Metabolism ; 29 : — Immediate effect of lesion of the ventromedial hypothalamic area upon glucose-induced insulin secretion in anaesthetized rats.
Diabetologia ; 13 : — Brain-derived neurotrophic factor modulates glucagon secretion from pancreatic alpha cells: its contribution to glucose metabolism. To learn more about Healthwise, visit Healthwise. Healthwise, Healthwise for every health decision, and the Healthwise logo are trademarks of Healthwise, Incorporated. How the Body Controls Blood Sugar. Topic Overview The bloodstream carries glucose-a type of sugar produced from the digestion of carbohydrates and other foods-to provide energy to cells throughout the body.
Current as of May 3, Current as of: May 3, Epinephrine also promotes the breakdown and release of fat nutrients that travel to the liver where they are converted into sugar and ketones. Cortisol is a steroid hormone also secreted from the adrenal gland. It makes fat and muscle cells resistant to the action of insulin, and enhances the production of glucose by the liver.
Under normal circumstances, cortisol counterbalances the action of insulin. Under stress or if a synthetic cortisol is given as a medication such as with prednisone therapy or cortisone injection , cortisol levels become elevated and you become insulin resistant.
When you have Type 1 diabetes, this means your may need to take more insulin to keep your blood sugar under control. Growth Hormone is released from the pituitary, which is a part of the brain. Like cortisol, growth hormone counterbalances the effect of insulin on muscle and fat cells. High levels of growth hormone cause resistance to the action of insulin.
The hyperglycemia and hyperinsulinemia caused by the over-stressed beta cells create their own failure. In type 2 diabetes, the continual loss of functioning beta cells shows up as a progressive hyperglycemia.
How would you explain insulin resistance differently to someone with type 1 diabetes and someone with type 2 diabetes? Together, insulin resistance and decreased insulin secretion lead to hyperglycemia, which causes most of the health problems in diabetes. The acute health problems—diabetic ketoacidosis and hyperosmolar hyperglycemic state—are metabolic disorders that are directly caused by an overload of glucose. In comparison, the chronic health problems—eye, heart, kidney, nerve, and wound problems—are tissue injury, a slow and progressive cellular damage caused by feeding tissues too much glucose ADA, Hyperglycemic damage to tissues is the result of glucose toxicity.
There are at least three distinct routes by which excess glucose injures tissues:. If you are attending a virtual event or viewing video content, you must meet the minimum participation requirement to proceed. If you think this message was received in error, please contact an administrator.
Return to Course Home. Fuels of the Body To appreciate the pathology of diabetes, it is important to understand how the body normally uses food for energy. Hormones of the Pancreas Regulation of blood glucose is largely done through the endocrine hormones of the pancreas, a beautiful balance of hormones achieved through a negative feedback loop. The glucose becomes syrupy in the bloodstream, intoxicating cells and competing with life-giving oxygen.
Optimal health requires that: When blood glucose concentrations are low, the liver is signaled to add glucose to the circulation. When blood glucose concentrations are high, the liver and the skeletal muscles are signaled to remove glucose from the circulation. Test Your Knowledge Glycogen is: A hormone produced in the pancreas. A polysaccharide that is stored in the liver.
Produced in the striated muscles when exercising. An energy reserve that is slow to mobilize in an emergency. Apply Your Knowledge If you want to lose weight, what fuel would you decrease in your diet and what fuels would you increase? Is a hormone that acts on the liver to convert excess glucose into glycogen.
Inhibits the uptake and use of glucose by skeletal muscles. Is manufactured and secreted by the alpha cells of the pancreas. Apply Your Knowledge How would you explain the function of insulin to your patient with diabetes? Test Your Knowledge Glucagon: Is a peptide hormone that is stored in the pancreas. Is used to treat hyperglycemia by increasing the uptake of glucose in muscles. Is a hormone that acts on the liver to convert glycogen back into glucose.
Stimulates the production of insulin. Apply Your Knowledge How is glucagon available by injection? Test Your Knowledge People with type 2 diabetes have: Insulin sensitivity, which is an over-reaction of cells to insulin. No beta cells in their pancreas and no circulating insulin at all. Chronic hypoglycemia.
Insulin resistance, which is a decreased response of cells to insulin. Apply Your Knowledge How would you explain to your patient what lifestyle behaviors create insulin resistance? Test Your Knowledge In type 2 diabetes: Beta cells in the pancreas cannot compensate for insulin resistance. The liver becomes overly sensitive to insulin. Glucose cannot be used as fuel by any cells in the body. Apply Your Knowledge How would you explain insulin resistance differently to someone with type 1 diabetes and someone with type 2 diabetes?
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