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Overview of blood glucose regulation and the consequences of dysregulation
1. Glucose ---- obligatory fuel for CNS and RBC’s
Liver Storage ----> ~100gms (~400kcals)
Whole body oxidation of glucose ------> ~160-200gms/day (basal
condition)
CNS ------> ~70 -75% (~120gms)
Consequences
Depletion of hepatic glycogen -----> Decrease CNS functioning
Responses:
De-novo synthesis (gluconeogenesis)
EAT
2. General regulation of plasma glucose
Pancreas -----> alpha and beta cells
Fig. 9-1 and 9-2 (Metab.)
3. Normal and abnormal plasma glucose levels -----> endocrine dysfunction/cell
response dysfunction
Fig 9-4 (Metab.)
4. Metabolic consequences of insulin insufficiency
Fig. 9-3 (Metab)
Types of Diabetes ------ Historical development of nomenclature
5. Pathologic states associated with diabetes
CAD
Peripheral neuropathy
PAD
Distal limb amputations
CRF
Retinopathy
Cataracts
6. Underlying mechanisms:
Glycosylation of proteins (Fig. 9-5 (Metab)) ----- membrane dysfunction
Polyol formation (lens accumulation of sorbitol)
7. Glycosylated hemoglobin -----> key marker for plasma glucose stability
Fig. 9-6 (Metab)
Glycogen Metabolism
1. Glycogen Storage ---- Hepatic and Skeletal Muscle Tissue
Volumes and Purpose ----> Overview (Table 12-2)
2. Plasma Membrane Transport
Protein transport Proteins (Fig 11-2 – Metab.)
GLUT 2 – Liver
GLUT 4 – Skeletal Muscle
Phosphorylating Enzymes
Glucokinase – Liver
Hexokinase – Skeletal Muscle
Note different sites of activation by insulin
3. Formation of Glycogen (Fig, 12-2 – Metab)
Glucose-6-Phosphatase (only in Liver) – WHY?
Optional pathways for G-6-P
4. Enzymatic Regulation of Glycogen Metabolism
Synthesis – Glycogen Synthase (Fig 12-4 Metab.)
Degradation – Glycogen Phosphorylase (Fig. 12-7 Metab)
Additional control of degradation by calcium (Fig. 12-8 Metab)
5. GLUT 4 translocation and Glucose uptake
Fig. 3-2 (Hargreaves)
Types of Diabetes ------ Historical development of nomenclature
6. Effects of Exercise (Fig. 2, 3, 4 – Christ-Roberts)
GLUT 4 Translocation
Sensitivity to Insulin
Glucose uptake by Skeletal Muscle
Adaptations to regular physical activity
7. The Type 2 Diabetic:
Is it insulin release?
Is it insulin receptors?
Is it down-regulation of GLUT 4 transporter synthesis and translocation
Adipocyte Metabolism and Fatty Acid Oxidation
1. Adipose Tissue
Volume and Purpose
General Concepts
Energy Storage
Energy Release
Mobilization
Transport
Plasma Membrane diffusion
Mitochondrion membrane transport
Beta Oxidation
Derivatives into Krebs Cycle and ETS
Contribution to power/anaerobic metabolism
Spot Reduction
2. Impact of Insulin
Hepatic Tissue (Glucose and aa’s ---> TG’s --> VLDL’s) (Fig 20-1 Metab.)
Adipocyte - LPL (Glucose ----> glycerol 3-P + FA’s ---> TG’s) (Fig. 20.6
Metab)
3. Impact of Glucagon and Epinephrine (Fig, 20-2, 20.6 – Metab)
Glucagon effect on Liver –----> Gluconeogenesis
Glucagon ---->effect on Adipocyte (HSL)
Epinephrine, and Glucocorticoid ---->effect on Adipocyte (HSL)
Subsequent uptake of FA’s by all tissues except brain and RBC’s
4. Fatty Acid Oxidation
Transport across the inner mitochondrial membrane (Fig, 20.7 Metab)
Role of Acyl Carnitine Transferase (CAT 1 and 2)
Role of Acyl Carnitine Translocase (CT)
5. Beta Oxidation (Fig. 20-8 Metab)
Key marker enzyme ---> B-HydroxyAcyl-CoA-DH (HAD)
6. Ketogenesis ---> starvation conditions (Fig. 20.11 Metab.)
Uptake by brain, skeletal muscle,…… hypoglycemia
Preservation of protein structures