Slideshow is from the University of Michigan Medical School's M2 Endocrine sequence View additional course materials on Open.Michigan: openmi.ch/med-M2Endo

1. Author(s): Arno Kumagai, M.D., 2009
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3. Islet Cell Hormones
And
Hormonal Regulation of Fuel Metabolism
M2-Endocrine Sequence
Arno K. Kumagai, M.D
Dept. of Internal Medicine
Winter 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
INSULIN
A. Kumagai

8. Insulin Action
www.hannal.co.kr

9. Insulin Actions
Mharrsch, Flickr
Insulin 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 is
completely dependent
on glucose for normal
metabolism until >5
days 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 Glucoenogenesis
and 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 Points
Understand:
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 Points
Understand:
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/CitationPolicy
Slide 4: Arno Kumagai
Slide 5: Dr. Thomas Caceci, Image found at http://education.vetmed.vt.edu/curriculum/vm8054/labs/labtoc.htm
Slide 6: Source Undetermined
Slide 7: Arno Kumagai
Slide 8: www.hannal.co.kr
Slide 9: Mharrsch, Flickr, http://www.flickr.com/photos/mharrsch/
Slide 10: Arno Kumagai
Slide 11: Arno Kumagai
Slide 12: Arno Kumagai
Slide 13: Arno Kumagai; Source Undetermined
Slide 14: Arno Kumagai
Slide 15: Arno Kumagai
Slide 16: Arno Kumagai
Slide 17: Source Undetermined
Slide 18: Arno Kumagai
Slide 19: Source Undetermined
Slide 20: Arno Kumagai
Slide 21: Source Undetermined