Hormonal Reg of Fuel Metabolism

Hormonal Reg of Fuel Metabolism

1. Insulin

   • Insulin is peptide hormone with chains A and B linked by disulfide bonds
   • Production of mature insulin: synthesis, cleavage in RER lumen, transport proinsulin to Golgi and storage vesicles cleavage --> insulin + C-peptie coprecipitation with Zn++ in storage vesicles
   • Insulin promotes glucose storage as glycogen and conversion of glucose to fat.
   • B- cells of pancreas
     • High [blood glucose]
       • Secrete Insulin
   • Action
     • Stimulates
       • Glucose
         • Uptake
           • From blood
           • In muscle cells
             • + GLUT-4
               • Major glucose transporter
           • In brain cells
             • Insulin independent
         • Utilization
           • In Liver
             • Insulin stimulates the utilization of glucose in the liver, but not glucose uptake
         • Storage
       • Fat
         • Synthesis
         • Storage
       • Protein
         • Synthesis
     • Inhibits
       • Glycogen
         • Breakdown
       • Fat
         • Mobilization
   • Response
     • Biphasic
       • Initial
         • Release from vesicles
       • Sustained
         • De novo synthesis
     • [Blood glucose] increase
       • For increases in plasma glucose concentrations up to 300 mg/dL, the normal increase in insulin release is proportional to the glucose level
       • Sugars stimulate a more rapid increase in blood sugar than complex carbs Fiber decreases glycemic index of foods (area under 2 hr glucose curve after feeding 50 g CHO portion)
       • 2-3x normal range
   • Reverse PKA Effects
     • + protein serine/threonine phosphatase
       • Reverses phosphorylation from PKA
       • Inhibits mobilization of glucose from glycogen
       • + glycogen synthase

2. Glucagon

   • 29 AA polypeptide hormone released by a-cells of pancreas Initial synthesis of proglucagon Plasma glucagon has half-life of 3-5 mins
   • Fasted State
     • Liver
       • Releases glucose
         • Maintains plasma levels
         • Mobilizes glycogen
       • Gluconeogenesis
         • AAs
           • Muscle Catabolism
     • Major Energy Source
       • Fatty Acids
         • TAGs
   • Secretion
     • Stimulated
       • Epinephrine
       • Cortisol
       • Exhaustive Exercise
       • Amino Acids
         • in normal, "mixed" meals, amino acids, especially lysine and arginine, increase (or potentiate) the insulin response to glucose.
         • Protein meal, no CHO
     • Inhibited
       • High [plasma glucose]
       • Insulin
   • Action
     • Targets
       • Liver
       • Adipocytes
       • NOT muscle
     • Stimulates
       • Glycogen breakdown
       • Gluconeogenesis
       • Glucose release
       • TAG hydrolysis
       • FA release
     • Inhibits
       • Glycogen synthesis
       • Fat storage
     • Increase cAMP
       • Activate PKA

3. Epinephrine

   • Synthesis
     • Response to stress
       • Adrenal Medulla
   • Action
     • Glycogen Mobilization
       • Liver
         • Blood Glucose
       • Muscle
         • glucose-P
           • ATP generation
     • Increase cAMP
       • Activate PKA
         • + phosphorylase kinase
           • + phosphorylase
             • Release glucose -P from glycogen
         • + lipase
           • Hydrolysis of stored fat
         • - glycogen synthase
           • First step in FA synthesis
           • inhibits glycogen synthesis
         • Insulin reverses effects

4. Glucocorticoids

   • Action
     • Stimulate fuel mobilization
       • Regulate gene transcription
       • Glycogen synthesis
         • Cortisol stimulates glycogen synthesis, then glucagon and epinephrine stimulate glycogen mobilization
     • Bind intracellular receptors
     • Mediate changes over long periods
       • Starvation
       • Sepsis
       • Stress