Long-term intake of a ketogenic diet enhances utilization of ketone bodies, a particularly energy-efficient substrate, during exercise. However, physiological adaptation to an extremely low-carbohydrate diet has been shown to upregulate pyruvate dehydrogenase kinase 4 (PDK4, a negative regulator of glycolytic flux) content in skeletal muscle, resulting in impaired high-intensity exercise capacity. This study aimed to examine the effects of a long-term ketogenic diet containing medium-chain triglycerides (MCTs) on endurance training-induced adaptations in ketolytic and glycolytic enzymes of rat skeletal muscle. Male Sprague-Dawley rats were placed on either a standard diet (CON), a long-chain triglyceride-containing ketogenic diet (LKD), or an MCT-containing ketogenic diet (MKD). Half the rats in each group performed a 2-h swimming exercise, 5 days a week, for 8 weeks. Endurance training significantly increased 3-oxoacid CoA transferase (OXCT, a ketolytic enzyme) protein content in epitrochlearis muscle tissue, and MKD intake additively enhanced endurance training–induced increases in OXCT protein content. LKD consumption substantially increased muscle PDK4 protein level. However, such PDK4 increases were not observed in the MKD-fed rats. In conclusion, long-term intake of ketogenic diets containing MCTs may additively enhance endurance training–induced increases in ketolytic capacity in skeletal muscle without exerting inhibitory effects on carbohydrate metabolism.
Long‐term endurance training for a relatively short duration (~1 h) is reported to increase pancreatic amylase activity in rats, suggesting that chronic exercise training enhances carbohydrate digestive capacity. However, it remains unknown whether longer exercise training duration results in greater adaptation in the pancreas and small intestine. Thus, this study aimed to examine the effects of long‐term endurance training for a longer duration on pancreatic amylase activity and intestinal glucose transporter content in rats. Male Sprague–Dawley rats were subjected to swimming exercise training for 1 h (Ex‐1h group) or 6 h (Ex‐6h group, two 3‐h sessions separated by 1 h of rest) each day, 5 days a week, for 6 weeks. Sedentary rats were used as a control (Con group). Total pancreatic amylase activity in the Ex‐6h group was significantly lower than that in the Con and Ex‐1h groups immediately after the last training session. After 24 h of recovery, total pancreatic amylase activity was significantly higher in the Ex‐1h group (~46%) than in the Con group, and a further increase was observed in the Ex‐6h group (~98%). In addition, the Ex‐6h group, but not the Ex‐1h group, showed significantly greater intestinal sodium‐dependent glucose transporter 1 (SGLT1) content compared with the Con group after 24 h of recovery. However, no significant difference was observed in glucose transporter 2 (GLUT2) content among the three groups. In conclusion, chronic endurance exercise training for a longer duration results in larger increases in pancreatic amylase activity and intestinal SGLT1 content in rats.
Background:
SGLT2i (sodium-glucose cotransporter 2 inhibitor), a class of anti-diabetic medications, is shown to reduce blood pressure (BP) in hypertensive patients with type 2 diabetes. Mechanisms underlying this action are unknown but SGLT2i-induced sympathoinhibition is thought to play a role. Whether SGLT2i reduces BP and sympathetic nerve activity (SNA) in a nondiabetic prehypertension model is unknown.
Methods:
Accordingly, we assessed changes in conscious BP using radiotelemetry and alterations in mean arterial pressure and renal SNA during simulated exercise in nondiabetic spontaneously hypertensive rats during chronic administration of a diet containing dapagliflozin (0.5 mg/kg per day) versus a control diet.
Results:
We found that dapagliflozin had no effect on fasting blood glucose, insulin, or hemoglobin A
1C
levels. However, dapagliflozin reduced BP in young (8-week old) spontaneously hypertensive rats as well as attenuated the age-related rise in BP in adult spontaneously hypertensive rat up to 17-weeks of age. The rises in mean arterial pressure and renal SNA during simulated exercise (exercise pressor reflex activation by hindlimb muscle contraction) were significantly reduced after 4 weeks of dapagliflozin (Δmean arterial pressure: 10±7 versus 25±14 mm Hg, Δrenal SNA: 31±17% versus 68±39%,
P
<0.05). Similarly, rises in mean arterial pressure and renal SNA during mechanoreflex stimulation by passive hindlimb stretching were also attenuated by dapagliflozin. Heart weight was significantly decreased in dapagliflozin compared with the control group.
Conclusions:
These data demonstrate a novel role for SGLT2i in reducing resting BP as well as the activity of skeletal muscle reflexes, independent of glycemic control. Our study may have important clinical implications for preventing hypertension and hypertensive heart disease in young prehypertensive individuals.
IntroductionEndogenous carbohydrate stores are limited and thus almost completely emptied within only a few hours of continuous submaximal 70 -80 maximal oxygen uptake exercise. The depletion of carbohydrate reserves is associated with onset of fatigue and impairment of exercise capacity 1 . Meanwhile, body fat deposits constitute another, much larger, source of fuel for exercise. It is well known that long-term endurance exercise training increases the expressions of mitochondrial enzymes, especially fatty acid oxidation FAO enzymes, in skeletal muscle 2 . Muscle pyruvate dehydrogenase kinase 4 PDK4 , which inactivates the pyruvate dehydrogenase complex and inhibits glycolytic flux, is also increased by endurance training 3 .
These results suggest that topical application of ibudilast while using 2 Week Pure lenses can improve subjective symptoms without influencing drug adsorption or lens morphology.
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