Title Page
Contents
1. Introduction 9
2. Literature review 13
2.1. Diabetes mellites 14
2.2. Diabetes-related sarcopenia 15
2.2.1. Sarcopenia and mitochondrial biogenesis 15
2.2.2. Sarcopenia and inflammation 16
2.2.3. Sarcopenia and the ubiquitin-proteasome system 16
2.2.4. Sarcopenia and endoplasmic reticulum stress 17
2.3. Correlation between sarcopenia and cognitive dysfunction 18
2.4. Ketogenic diet (KD) and β-hydroxybutyrate (BHB) 18
2.4.1. Effects of KD and BHB on glucose control 19
2.4.2. Effects of KD and BHB on muscle mass and function 19
2.4.3. Effects of KD and BHB on cognitive function 20
2.4.4. Effects of KD and BHB on lipid metabolism 21
3. Materials and methods 22
3.1. Animal model and treatments 23
3.2. Measurement of glucose tolerance 27
3.3. Measurement of ketone bodies 27
3.4. Behavioral-cognitive function test 27
3.4.1. Grip strength test 27
3.4.2. Y-maze test 28
3.5. Analysis of skeletal muscle histology 28
3.6. Gene expression analysis 29
3.7. Statistical analysis 29
4. Results 31
4.1. Body weights and food intake 32
4.2. Tissue weights 34
4.3. Glucose tolerance and BHB concentration 36
4.4. Muscle strength 38
4.5. Cognitive function 40
4.6. Morphology of gastrocnemius muscle 42
4.6.1. H&E-stained gastrocnemius muscle morphology 42
4.6.2. Cross-sectional area of muscle fibers in gastrocnemius muscle 44
4.7. Inflammation-related genes expression in gastrocnemius muscle 46
4.8. Endoplasmic reticulum stress-related genes expression in gastrocnemius muscle 48
5. Discussion 50
6. References 55
국문초록 68
Table 1. Composition of diets 26
Table 2. Primer sequences for real-time reverse transcription polymerase chain reaction 30
Table 3. Effects of KD and BHB supplementation on tissue weights 35
Figure 1. Research hypothesis 12
Figure 2. Experimental design 25
Figure 3. Body weights and food intake 33
Figure 4. Glucose tolerance and BHB concentration 37
Figure 5. Grip strength tests 39
Figure 6. Y-maze test 41
Figure 7. H&E-stained gastrocnemius muscle morphology 43
Figure 8. Average of fiber size and distribution 45
Figure 9. Inflammation-related genes expression in gastrocnemius muscle 47
Figure 10. Endoplasmic reticulum stress-related genes expression in gastrocnemius muscle 49