Caffeine (1,3,7-trimethylxanthine) has been implicated in the regulation of glucose and lipid metabolism including actions such as insulin-independent glucose transport, glucose transporter 4 expression, and fatty acid utilization in skeletal muscle. These effects are similar to the exercise-induced and 5'adenosine monophosphate-activated protein kinase (AMPK)-mediated metabolic changes in skeletal muscle, suggesting that caffeine is involved in the regulation of muscle metabolism through AMPK activation. We explored whether caffeine acts on skeletal muscle to stimulate AMPK. Incubation of rat epitrochlearis and soleus muscles with Krebs buffer containing caffeine (> or =3 mmol/L, > or =15 minutes) increased the phosphorylation of AMPKalpha Thr(172), an essential step for full kinase activation, and acetyl-coenzyme A carboxylase Ser(79), a downstream target of AMPK, in dose- and time-dependent manners. Analysis of isoform-specific AMPK activity revealed that both AMPKalpha1 and alpha2 activities increased significantly. This enzyme activation was associated with a reduction in phosphocreatine content and an increased rate of 3-O-methyl-d-glucose transport activity in the absence of insulin. These results suggest that caffeine has similar actions to exercise by acutely stimulating skeletal muscle AMPK activity and insulin-independent glucose transport with a reduction of the intracellular energy status.

Our results suggest that of the two α isoforms of AMPK, AMPKα1 is predominantly activated by caffeine via an energy-independent mechanism and that the activation of AMPKα1 increases glucose transport and ACC phosphorylation in skeletal muscle.

The present study aimed to examine whether a single bout of percutaneous low-frequency electrical muscle stimulation (EMS) can attenuate postprandial hyperglycemia in human subjects. Ten obese and 4 pre-obese Japanese men participated in two experimental sessions; one involved 20 min of EMS just after a breakfast (EMS trial) and the other involved complete rest after a breakfast (Control trial). In each trial, blood samples were taken before and at 30, 60, 90, and 120 minutes after the meal. Blood lactate concentration and respiratory gas exchange were measured during EMS and at complete rest after a meal in the EMS and Control trials, respectively. The results showed that the postprandial hyperglycemia was signiˆcantly attenuated in the EMS trial (Pº0.05). Also, the postprandial increase of blood insulin was signiˆcantly attenuated in the EMS trial (Pº0.05). However, blood triglyceride was not aŠected by EMS. In addition, blood lactate signiˆcantly increased (Pº0.05), and the respiratory quotient tended to elevate during EMS. These results demonstrate that EMS can be an eŠective method to attenuate postprandial hyperglycemia by enhancing glucose metabolism in contracted muscles.

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We report a rare complication of a secondary malignant solid tumor in two patients with non-Hodgkin's malignant lymphoma who developed lung adenocarcinoma after treatments with combination chemotherapies. The first was a case of primary malignant lymphoma of the cervical spinal cord which had been previously treated with radiation to the spinal lesion and combination chemotherapies and entered complete remission. The patient was further treated for relapse with autologous bone marrow transplantation preconditioned with high-dose chemotherapy. Lung adenocarcinoma developed 5.5 years after the initial diagnosis. The second case of malignant lymphoma of lymph nodes did not respond to conventional combination chemotherapies and did not enter remission. Lung adenocarcinoma developed 1 year after the initial diagnosis. The two patients died of lung carcinoma. The clinical profiles of these cases are presented and the causal relationship of primary malignant neoplasms to the second malignant neoplasms is discussed.