03.04.09: insulin action
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Author(s): Arno Kumagai, M.D., 2009 License: Unless otherwise noted, this material is made available under the terms of the Creative Commons Attribution–Noncommercial–Share Alike 3.0 License: http://creativecommons.org/licenses/by-nc-sa/3.0/
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Islet Cell Hormones
And
Hormonal Regulation of Fuel Metabolism
M2-Endocrine Sequence Arno K. Kumagai, M.D
Dept. of Internal Medicine
Winter 2009
Normal Physiology
ISLET CELL HORMONES
Beta Cells: INSULIN (AND AMYLIN)
Alpha Cells: GLUCAGON
A. Kumagai
Normal Physiology
ISLET CELL HORMONES
Beta Cells: INSULIN
(AND AMYLIN)
Alpha Cells: GLUCAGON
Image found at Dr. Thomas Caceci
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
Normal Insulin Physiology
STIMULI FOR INSULIN SECRETION:
GLUCOSE Amino Acids Fatty Acids
INSULIN
A. Kumagai
Insulin Action
www.hannal.co.kr
Insulin Actions
Insulin stores stuff… Mharrsch, Flickr
Insulin Action
SKELETAL MUSCLE • Increases glucose
transport • Increases glycogen
synthesis • Inhibits
gluconeogenesis
FAT • Increases
glucose transport • Increases
lipogenesis • Inhibits lipolysis
• Increases glycogen synthesis
• Increases glycolysis • Inhibits
gluconeogenesis
A. Kumagai
Normal Glucose Metabolism
GLUCOSE SUPPLY! GLUCOSE DEMAND!
BLOOD GLUCOSE70-120 mg/dL
BRAIN!
Insulin-independent tissues!
COKEDIET!
(-)! INSULIN!
Hepatic glucose production!
(+)!INSULIN!
Insulin-dependent tissues!
MUSCLE!
A. Kumagai
Normal Glucose Metabolism: The Fasting State or “Feeding the Head”
GLUCOSE SUPPLY! GLUCOSE DEMAND!
BLOOD GLUCOSE70-120 mg/dL
(+)!(-)! INSULIN! INSULIN!
BRAIN!
Insulin-independent tissues!
Hepatic glucose
production!
DIET! COKE
Insulin-dependent tissues!
MUSCLE!
A. Kumagai
Metabolic Changes During Fasting
Long term - Lipid mobilization!
Short term - Glycogen mobilization!
!
Intermediate - Gluconeo-genesis!
BRAIN!
The adult brain is completely dependent on glucose for normal metabolism until >5 days into a fast
The Brain = Obligate Glucose Consumer
Source Undetermined
(Brain) A. Kumagai
Normal Glucose Metabolism: The Fed State
GLUCOSE SUPPLY! GLUCOSE DEMAND!
BLOOD GLUCOSE70-120 mg/dL
(+)!(-)! INSULIN! INSULIN!
BRAIN!
Insulin-independent tissues!
COKEDIET!
Hepatic glucose production!
LiverMUSCLE!
A. Kumagai
INSULIN-GLUCAGON RELATIONSHIPS
INSULIN! GLUCAGON!
Glycogenesis and decreased blood glucose
Glucoenogenesis and increased blood glucose
STORAGE! MOBILIZATION!
A. Kumagai
Insulin Action
• Increases glycogen synthesis
• Increases glycolysis • Inhibits
gluconeogenesis
SKELETAL MUSCLE • Increases glucose
transport • Increases glycogen
synthesis • Inhibits
gluconeogenesis
FAT • Increases
glucose transport • Increases
lipogenesis • Inhibits lipolysis
A. Kumagai
Insulin-regulated steps in muscle carbohydrate metabolism!
Facilitated !glucose transport!
GLUT4!Hexokinase!
Glycogen synthase!
Glycogen synthase P!inactive!
active!
PFK!
Glucose-FA cycle!
Amino acids! AA Protein! (Citrate inhib PKF accum hexose P!reduce conc gradient for glucose entry)!
= insulin-sensitive!
(+)!I!
(+)!I!
(-)!I!
I!
Source Undetermined
Insulin Action
• Increases glycogen synthesis
• Increases glycolysis • Inhibits
gluconeogenesis
SKELETAL MUSCLE • Increases glucose
transport • Increases glycogen
synthesis • Inhibits
gluconeogenesis
FAT • Increases
glucose transport • Increases
lipogenesis • Inhibits lipolysis
A. Kumagai
Carbohydrate Metabolism in Hepatocytes!Insulin inhibits glucose production!
Insulin!Stimulates !glycogen storage!
Insulin!inhibits!Glycogen!breakdown!
Source Undetermined
Insulin Action
• Increases glycogen synthesis
• Increases glycolysis • Inhibits
gluconeogenesis
SKELETAL MUSCLE • Increases glucose
transport • Increases glycogen
synthesis • Inhibits
gluconeogenesis
FAT • Increases
glucose transport • Increases
lipogenesis • Inhibits lipolysis
A. Kumagai
Insulin-regulated carbohydrate metabolism: adipocyte!
Facilitated !glucose transport!
PDH! ACC!Lipogenesis!
Glycogen synthase!
Lipolysis!
HSL!
LPL!
Insulin inhibits lipolysis by stimulating lipoprotein
lipase (LPL) and inhibiting hormone-sensitive lipase
(HSL)!
GLUT4!
I!(+)! (-)!
Source Undetermined
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.
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).
Additional Source Information for more information see: http://open.umich.edu/wiki/CitationPolicy
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