Medium-chain triglycerides (8:0 and 10:0) increase muscle mass and function in frail older adults: a combined data analysis of clinical trials

BackgroundThree clinical trials have examined the chronic effects of medium-chain triglycerides (MCTs) on muscle mass and function in frail older adults (mean age 85 years old). However, significant increases in muscle mass and some muscle function relative to long-chain triglycerides (LCTs) have yet to be shown, possibly due to the small number of participants in each trial.ObjectiveWe re-analyzed these previous clinical trials to clarify whether MCT supplementation can increase muscle mass and function.AnalysisAfter adding post hoc tests to the original report, we compared changes in measurement between the MCT and LCT groups in the first 2 trials and conducted a combined data analysis.MethodsIn a combined data analysis, changes from baseline in measurements at the 3 months intervention in the MCTs- and LCTs-containing groups were assessed by analysis of covariance adjusted for baseline values of each measurement, age, sex, BMI, allocation to trial, habitual intakes in energy, protein, leucine, octanoic acid, decanoic acid, and vitamin D during the baseline period. The Mann–Whitney U test was used to analyze data on right and left knee extension times.ResultsMCT supplementation for 3 months increased muscle function relative to LCT supplementation with and without an L-leucine (1.2 g) and vitamin D (cholecalciferol, 20 μg)-enriched supplement. In a combined data analysis (n = 29 in MCTs, n = 27 in LCTs), relative to supplementation with 6 g LCTs/day, supplementation with 6 g MCTs/day at dinner for 3 months significantly increased body weight (adjusted mean change from baseline: MCTs 1.2 vs. LCTs 0.2 kg, p = 0.023), right arm muscle area (MCTs 1.4 vs. LCTs-0.7 cm2, p = 0.002), left calf circumference (p = 0.015), right-hand grip strength (MCTs 1.6 vs. LCTs 0.3 kg, p = 0.017), right knee extension time (p = 0.021), left knee extension time (p = 0.034), walking speed (p = 0.002), and number of iterations in leg open and close test (p < 0.001) and decreased right triceps skinfold thickness (p = 0.016).ConclusionIn frail older adults, supplementation for 3 months with a low dose (6 g/day) of MCTs (C8:0 and C10:0) increased muscle mass and function. These findings indicate the potential for the practical use of MCTs in daily life in treating sarcopenia

Influence of Amines in the Brain and Gastric Wall on Development of Stress Ulcers

With a view to examining the influence of amines in the brain and gastric wall on the development of stress ulcers, the authors loaded rats with the stress of cold restraint after administration of the inhibitory agents of produce and metabolism of amines, and the following findings were obtained. 1. Noradrenalin contents in the brain were significantly reduced after stress. The reduction relatively induced vagotonia and developed ulcers. Accordingly, noradrenalin in the brain associates with the development of stress ulcers. 2. Serotonin contents in the brain were increased significantly after stress, unlike the changes of the noradrenalin contents. But serotonin in the brain was not associated with the development of stress ulcers. 3. Histamine and serotonin contents in the gastric wall were reduced significantly after stress and both amines were associated with the development of stress ulcers. 4. Either of histamine or serotonin in the gastric wall was not be able to be the main cause on the development of stress ulcers, and their association was almost the same degree

Gastric Mucosal Lesions in Cases of Nonshunting Procedures for Esophageal Varices

Gastric mucosal lesions in 74 patients with esophageal varices for whom the nonshunting procedure was given in our institute from 1973 to 1983 were studied. Out of 9 patients of operative death, the direct cause of death in 2 patients was acute gastric mucosal lesion (AGML), and both patients belonged to Child C according to Child's Classification. The rate of complication of gastric mucosal lesion before operation was 42%, while it was 64% after operation, and all cases were complicated with liver cirrhosis. Among 31 cases in whom the condition before and after operation in the same case was compared, and found that gastric mucosal lesions were aggravated after operation in 12 patients (39%). The rate of post-operative aggravation of gastric mucosal lesions classified by the surgical formula was 18.8% of esophageal transection, and in comparison Hassab's operation was a high as 61.1%. In patients with liver cirrhosis, the defensive factors of the gastric mucosa had been reduced. Hassab's operation which changes the gastric mucosal blood flow by periesophago-gastric devascularization has a high possibility of aggravating gastric mucosal lesions

Surgical Treatment for Insulinoma: a Study of 6 Cases

The authors treated six patients with insulinoma in our department during a period up to 1984, and performed seven operations including one re-operation. In this paper, the results of our study of the clinical symptoms, diagnosis and surgical formula in these cases are presented. Selective angiography and percutaneous transhepatic portal venous sampling (PTPVS) proved useful for pre-operative tumor localization diagnosis. Blood glucose monitoring during operation became a good index for the selection of the surgical formula. In the cases of surfacial and single tumors, enucleation alone was able to obtain satisfactory surgical results. In the cases, however, when re-operative, deep or multiple tumors were suspected, staged distal pancreatectomy under blood glucose monitoring was considered to be indicated. It was therefore thought that the preservation of the pancreas should be made as far as possible

Experimental Studies on Acute Gastric Mucosal Lesion Involved with Obstructive Jaundice: Mainly on the Changes of Amine Contents in the Gastric Mucosa on Cold Restraint Stress

The authors gave load of cold restraint stress to rats with obstructive jaundice and those on which biliary drainage was performed in order to examine the incidence of AGML, amine contents in the gastric mucosa, and gastric mucosal microcirculation, and the following results were obtained: 1) The incidence of AGML in the 3,4-week group of rats with obstructive jaundice and in the 4-week group of rats with biliary drainage after cold restraint for 30 min was increased markedly by 78% for each as compared with 22% in the control group. 2) The contents of histamine and serotonin in the gastric mucosa in the control group showed no significant change after cold restraint for 30 min, whereas the contents of both amines in the 3,4-week group of rats with obstructive jaundice and in the 4-week group of rats with biliary drainage were, respectively, significantly decreased after cold restraint. 3) Gastric mucosal microcirculation in the control group was prevented rather successfully, whereas that in the 4-week group of rats with obstructive jaundice after cold restraint for 30 min developed disturbance of gastric mucosal microcirculation due to congestion

A Comparison of Pancreatectomy and Pancreatic Duct Drainage in Chronic Pancreatitis

Surgical therapy was performed in 25 cases of chronic pancreatitis at the Second Department of Surgery, Hiroshima University School of Medicine from January 1973 to October 1984. Thirteen cases were considered related to the excessive intake of alcoholic drinks, 2 cases each to acute pancreatitis and gall stones, and 8 cases to unknown etiology. Complication of pancreatic stone and marked dilatation or partial constriction of the pancreatic duct were observed in 11 of the 25 cases. Pancreaticoduodenectomy was performed in 7 cases, distal pancreatectomy in 8 cases, longitudinal pancreaticojejunostomy in 6 cases, and pancreaticoplasty in 2 cases, and biliary surgery in 2 cases. Out of 21 cases with abdominal pains, pain disappeared in 12 cases, improved in 6 cases and remained uncharged in 3 cases, the effect from surgery being almost satisfactory. No difference was observed in the effect between the surgical procedure as described above. Endocrine function tests with 50 g OGTT revealed improvement in 2 cases and aggravation in another two cases. The function remained unchanged before and after operation in the remaining 21 cases. Pancreatic exocrine function tests with PFD revealed almost no changes before and after operation and no difference between the surgical procedures. Pancreatic exocrine function was found correlated with the advanced conditions of pancreatic fibrosis rather then with the surgical procedures. Cases with less advanced fibrosis maintained the function in a more satisfactory condition both before and after operation. There occurred no cases of death directory related to operation. Four cases of death, no relating to operation itself, were observed in the pancreatectomy group. Twenty cases are now under rehabilitated conditions. Results of our surgical treatment for chronic pancreatitis are almost satisfactory in respect to pain-relieving effect but unsatisfactory in respect to improvement of the endocrine and exocrine function. It may be necessary to consider surgical operation at an early stage before the aggravation of fibrosis, because various types of drainage procedures that aim at preserving the pancreatic tissue and reducing the pancreatic duct pressure are logically capable of improving pancreatic functions

〔総説〕サルコペニア: 運動による予防機序

Sarcopenia is a syndrome characterized by loss of skeletal muscle mass, strength, and function that occurs as a consequence of aging. Muscle mass represents a main determinant of muscle strength and has been strongly associated with performance in activities of daily living and the level of independence in the elderly. The decline in the total number of muscle fibers and specific atrophy of type II fibers contributes to the loss of skeletal muscles. Both endurance exercise and resistance training can delay the onset of sarcopenia via different mechanisms. Endurance exercise training improves muscle function by increases in mitochondrial and capillary number and eventually enhances exercise performance. Resistance training activates satellite cells around type II fibers and protein synthesis in myocytes. Increased muscle mass may prevent fat accumulation via secretion of myokines in skeletal muscles. The molecular mechanisms of both types of exercise to delay the onset of sarcopenia are summarized

Surgical Treatment of Pancreatic Cysts: Review of 21 Cases

Twenty one patients with the pancreatic cyst on whom operation was given in our department from 1965 to 1984 were divided into those with the inflammatory cyst (16 cases) and with the neoplastic cyst (5 cases), and the surgical results were examined. The surgical formulas of the inflammatory cyst were further divided into 9 cases of internal drainage of the cyst into the gastrointestinal tract, 1 case of external drainage, and 6 cases of cyst excision together with the resection of the pancreas, and the results were rather satisfactory. On the other hand, the cases of the neoplastic cyst were divided into 2 cases of cystadenocarcinoma, 1 case of cystadenoma and 2 cases of mucinous adenocarcinoma. The contents in the cyst were all mucinous. It is considered that, when the contents of the pancreatic cyst are mucinous, its malignant potential is high. Since examination during operation is often insufficient, we have been trying to recommend resection so far as possible

Induction of glucose uptake in skeletal muscle by central leptin is mediated by muscle β2-adrenergic receptor but not by AMPK

Leptin increases glucose uptake and fatty acid oxidation (FAO) in red-type skeletal muscle. However, the mechanism remains unknown. We have investigated the role of β2-adrenergic receptor (AR), the major β-AR isoform in skeletal muscle, and AMPK in leptin-induced muscle glucose uptake of mice. Leptin injection into the ventromedial hypothalamus (VMH) increased 2-deoxy-D-glucose (2DG) uptake in red-type skeletal muscle in wild-type (WT) mice accompanied with increased phosphorylation of the insulin receptor (IR) and Akt as well as of norepinephrine (NE) turnover in the muscle. Leptin-induced 2DG uptake was not observed in β-AR-deficient (β-less) mice despite that AMPK phosphorylation was increased in the muscle. Forced expression of β2-AR in the unilateral hind limb of β-less mice restored leptin-induced glucose uptake and enhancement of insulin signalling in red-type skeletal muscle. Leptin increased 2DG uptake and enhanced insulin signalling in red-type skeletal muscle of mice expressing a dominant negative form of AMPK (DN-AMPK) in skeletal muscle. Thus, leptin increases glucose uptake and enhances insulin signalling in red-type skeletal muscle via activation of sympathetic nerves and β2-AR in muscle and in a manner independent of muscle AMPK

Increased Systemic Glucose Tolerance with Increased Muscle Glucose Uptake in Transgenic Mice Overexpressing RXRγ in Skeletal Muscle

BACKGROUND: Retinoid X receptor (RXR) γ is a nuclear receptor-type transcription factor expressed mostly in skeletal muscle, and regulated by nutritional conditions. Previously, we established transgenic mice overexpressing RXRγ in skeletal muscle (RXRγ mice), which showed lower blood glucose than the control mice. Here we investigated their glucose metabolism. METHODOLOGY/PRINCIPAL FINDINGS: RXRγ mice were subjected to glucose and insulin tolerance tests, and glucose transporter expression levels, hyperinsulinemic-euglycemic clamp and glucose uptake were analyzed. Microarray and bioinformatics analyses were done. The glucose tolerance test revealed higher glucose disposal in RXRγ mice than in control mice, but insulin tolerance test revealed no difference in the insulin-induced hypoglycemic response. In the hyperinsulinemic-euglycemic clamp study, the basal glucose disposal rate was higher in RXRγ mice than in control mice, indicating an insulin-independent increase in glucose uptake. There was no difference in the rate of glucose infusion needed to maintain euglycemia (glucose infusion rate) between the RXRγ and control mice, which is consistent with the result of the insulin tolerance test. Skeletal muscle from RXRγ mice showed increased Glut1 expression, with increased glucose uptake, in an insulin-independent manner. Moreover, we performed in vivo luciferase reporter analysis using Glut1 promoter (Glut1-Luc). Combination of RXRγ and PPARδ resulted in an increase in Glut1-Luc activity in skeletal muscle in vivo. Microarray data showed that RXRγ overexpression increased a diverse set of genes, including glucose metabolism genes, whose promoter contained putative PPAR-binding motifs. CONCLUSIONS/SIGNIFICANCE: Systemic glucose metabolism was increased in transgenic mice overexpressing RXRγ. The enhanced glucose tolerance in RXRγ mice may be mediated at least in part by increased Glut1 in skeletal muscle. These results show the importance of skeletal muscle gene regulation in systemic glucose metabolism. Increasing RXRγ expression may be a novel therapeutic strategy against type 2 diabetes