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03.04.09: Insulin Action
03.04.09: Insulin Action
03.04.09: Insulin Action
03.04.09: Insulin Action
03.04.09: Insulin Action
03.04.09: Insulin Action
03.04.09: Insulin Action
03.04.09: Insulin Action
03.04.09: Insulin Action
03.04.09: Insulin Action
03.04.09: Insulin Action
03.04.09: Insulin Action
03.04.09: Insulin Action
03.04.09: Insulin Action
03.04.09: Insulin Action
03.04.09: Insulin Action
03.04.09: Insulin Action
03.04.09: Insulin Action
03.04.09: Insulin Action
03.04.09: Insulin Action
03.04.09: Insulin Action
03.04.09: Insulin Action
03.04.09: Insulin Action
03.04.09: Insulin Action
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03.04.09: Insulin Action

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Slideshow is from the University of Michigan Medical School's M2 Endocrine sequence …

Slideshow is from the University of Michigan Medical School's M2 Endocrine sequence

View additional course materials on Open.Michigan:
openmi.ch/med-M2Endo

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  • 1. Author(s): Arno Kumagai, M.D., 2009License: Unless otherwise noted, this material is made available under the terms ofthe Creative Commons Attribution–Noncommercial–Share Alike 3.0 License:http://creativecommons.org/licenses/by-nc-sa/3.0/We have reviewed this material in accordance with U.S. Copyright Law and have tried to maximize your ability to use,share, and adapt it. The citation key on the following slide provides information about how you may share and adapt thismaterial.Copyright holders of content included in this material should contact open.michigan@umich.edu with any questions,corrections, or clarification regarding the use of content.For more information about how to cite these materials visit http://open.umich.edu/education/about/terms-of-use.Any medical information in this material is intended to inform and educate and is not a tool for self-diagnosis or areplacement for medical evaluation, advice, diagnosis or treatment by a healthcare professional. Please speak to yourphysician if you have questions about your medical condition.Viewer discretion is advised: Some medical content is graphic and may not be suitable for all viewers.
  • 2. Citation Key for more information see: http://open.umich.edu/wiki/CitationPolicyUse + Share + Adapt { Content the copyright holder, author, or law permits you to use, share and adapt. } Public Domain – Government: Works that are produced by the U.S. Government. (17 USC § 105) Public Domain – Expired: Works that are no longer protected due to an expired copyright term. Public Domain – Self Dedicated: Works that a copyright holder has dedicated to the public domain. Creative Commons – Zero Waiver Creative Commons – Attribution License Creative Commons – Attribution Share Alike License Creative Commons – Attribution Noncommercial License Creative Commons – Attribution Noncommercial Share Alike License GNU – Free Documentation LicenseMake Your Own Assessment { Content Open.Michigan believes can be used, shared, and adapted because it is ineligible for copyright. } Public Domain – Ineligible: Works that are ineligible for copyright protection in the U.S. (17 USC § 102(b)) *laws in your jurisdiction may differ { Content Open.Michigan has used under a Fair Use determination. } Fair Use: Use of works that is determined to be Fair consistent with the U.S. Copyright Act. (17 USC § 107) *laws in your jurisdiction may differ Our determination DOES NOT mean that all uses of this 3rd-party content are Fair Uses and we DO NOT guarantee that your use of the content is Fair. To use this content you should do your own independent analysis to determine whether or not your use will be Fair.
  • 3. Islet Cell Hormones And Hormonal Regulation of Fuel Metabolism M2-Endocrine Sequence Arno K. Kumagai, M.D Dept. of Internal MedicineWinter 2009
  • 4. Normal Physiology ISLET CELL HORMONES Alpha Cells: GLUCAGON Beta Cells: INSULIN (AND AMYLIN)A. Kumagai
  • 5. Normal Physiology ISLET CELL HORMONES Alpha Cells: Beta Cells: GLUCAGON INSULIN (AND AMYLIN)Image found at Dr. Thomas Caceci
  • 6. Response to a meal!Islet hormone secretion varies!with circulating glucose levels!Meal increases: !Glucose! increased insulin! decreased glucagon! Amino acids, FA! increased insulin! Source Undetermined
  • 7. Normal Insulin Physiology STIMULI FOR INSULIN SECRETION: GLUCOSE Amino Acids Fatty Acids INSULINA. Kumagai
  • 8. Insulin Actionwww.hannal.co.kr
  • 9. Insulin ActionsMharrsch, FlickrInsulin stores stuff…
  • 10. Insulin Action SKELETAL MUSCLE•  Increases glycogen •  Increases glucose synthesis•  Increases glycolysis FAT transport •  Increases •  Increases glycogen•  Inhibits glucose transport synthesis gluconeogenesis •  Increases •  Inhibits lipogenesis gluconeogenesis •  Inhibits lipolysis A. Kumagai
  • 11. Normal Glucose Metabolism GLUCOSE SUPPLY! GLUCOSE DEMAND! DIET! BRAIN! COKE BLOOD Insulin-independent tissues! GLUCOSE 70-120 mg/dL MUSCLE! Hepatic glucose production! (+)! (-)! INSULIN! INSULIN! Insulin-dependent tissues!A. Kumagai
  • 12. Normal Glucose Metabolism: The Fasting State or Feeding the Head GLUCOSE SUPPLY! GLUCOSE DEMAND! DIET! COKE BRAIN! BLOOD Insulin-independent tissues! GLUCOSE 70-120 mg/dL MUSCLE! Hepatic glucose production! (+)! (-)! INSULIN! INSULIN! Insulin-dependent tissues!A. Kumagai
  • 13. The Brain = Obligate Glucose Consumer Metabolic Changes During Fasting BRAIN!The adult brain iscompletely dependenton glucose for normalmetabolism until >5days into a fast Short term - Intermediate - Long term - Glycogen Gluconeo- Lipid mobilization! genesis! mobilization! ! Source Undetermined (Brain) A. Kumagai
  • 14. Normal Glucose Metabolism: The Fed State GLUCOSE SUPPLY! GLUCOSE DEMAND!DIET! BRAIN! COKE BLOOD Insulin-independent tissues! GLUCOSE 70-120 mg/dL Liver Hepatic glucose MUSCLE! production! (-)! INSULIN! INSULIN! (+)! A. Kumagai
  • 15. INSULIN-GLUCAGON RELATIONSHIPS STORAGE! MOBILIZATION! INSULIN! GLUCAGON! Glycogenesis Glucoenogenesisand decreased and increased blood glucose blood glucose A. Kumagai
  • 16. Insulin Action SKELETAL MUSCLE•  Increases glycogen •  Increases glucose synthesis•  Increases glycolysis FAT transport •  Increases •  Increases glycogen•  Inhibits glucose transport synthesis gluconeogenesis •  Increases •  Inhibits lipogenesis gluconeogenesis •  Inhibits lipolysis A. Kumagai
  • 17. Insulin-regulated steps in muscle carbohydrate metabolism! I! = insulin-sensitive! Glycogen synthase P! Facilitated ! inactive! glucose transport! I! Glycogen synthase! (+)! GLUT4! active ! Hexokinase! I! (+)! PFK! Glucose-FA cycle! I! (-)! Amino acids! AA Protein! (Citrate inhib PKF accum hexose P! reduce conc gradient for glucose entry)! Source Undetermined
  • 18. Insulin Action SKELETAL MUSCLE•  Increases glycogen •  Increases glucose synthesis•  Increases glycolysis FAT transport •  Increases •  Increases glycogen•  Inhibits glucose transport synthesis gluconeogenesis •  Increases •  Inhibits lipogenesis gluconeogenesis •  Inhibits lipolysis A. Kumagai
  • 19. Carbohydrate Metabolism in Hepatocytes! Insulin inhibits glucose production! Insulin!Insulin! inhibits!Stimulates ! Glycogen!glycogen storage! breakdown! Source Undetermined
  • 20. Insulin Action SKELETAL MUSCLE•  Increases glycogen •  Increases glucose synthesis•  Increases glycolysis FAT transport •  Increases •  Increases glycogen•  Inhibits glucose transport synthesis gluconeogenesis •  Increases •  Inhibits lipogenesis gluconeogenesis •  Inhibits lipolysis A. Kumagai
  • 21. Insulin-regulated carbohydrate metabolism: adipocyte! Facilitated ! Glycogen synthase! glucose transport! Insulin inhibits lipolysis by GLUT4! stimulating lipoprotein lipase (LPL) and inhibiting hormone-sensitive lipase (HSL) ! Lipogenesis! PDH! ACC! Lipolysis! I! ! HSL (+)! (-)! LPL! Source Undetermined
  • 22. Fuel Metabolism: Take-Home PointsUnderstand:1.  That insulin binding to its receptor initiates a cascade of signaling pathways that results in translocation of the insulin-sensitive GLUT4 to the plasma membrane and increased glucose uptake.2.  The changes in insulin secretion in fasting and fed states and the physiologic rationale for preserving brain glucose uptake.
  • 23. Fuel Metabolism: Take-Home PointsUnderstand:3.  The actions of insulin on skeletal muscle, liver, and fat.4.  The biochemistry: understand that insulin stores (e.g., stimulates glycogen synthase and lipoprotein lipase) and inhibits catabolism (e.g., inhibits HSL).
  • 24. Additional Source Information for more information see: http://open.umich.edu/wiki/CitationPolicySlide 4: Arno KumagaiSlide 5: Dr. Thomas Caceci, Image found at http://education.vetmed.vt.edu/curriculum/vm8054/labs/labtoc.htmSlide 6: Source UndeterminedSlide 7: Arno KumagaiSlide 8: www.hannal.co.krSlide 9: Mharrsch, Flickr, http://www.flickr.com/photos/mharrsch/Slide 10: Arno KumagaiSlide 11: Arno KumagaiSlide 12: Arno KumagaiSlide 13: Arno Kumagai; Source UndeterminedSlide 14: Arno KumagaiSlide 15: Arno KumagaiSlide 16: Arno KumagaiSlide 17: Source UndeterminedSlide 18: Arno KumagaiSlide 19: Source UndeterminedSlide 20: Arno KumagaiSlide 21: Source Undetermined

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