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Data from the use of activators and inhibitors of the AMP-activated protein kinase (AMPK) suggest that AMPK increases sensitivity of glucose transport to stimulation by insulin in muscle cells. We assayed insulin action after adenoviral (Ad) transduction of constitutively active (CA; a truncated form of AMPK[[alpha].sub.1]) and dominant-negative (DN; which depletes endogenous AMPK[alpha]) forms of AMPK[alpha] (Ad-AMPK[alpha]-CA and Ad-AMPK[alpha]-DN, respectively) into [C.sub.2][C.sub.12] myotubes. Compared with control (Adgreen fluorescent protein), Ad-AMPK-CA increased the ability of insulin to stimulate glucose transport. The increased insulin action in cells expressing AMPK-CA was suppressed by compound C (an AMPK inhibitor). Exposure of cells to 5-aminoimidazole-4-carboxamide-l[beta]-D-ribofuranoside (an AMPK activator) increased insulin action in uninfected myotubes and myotubes transduced with green fluorescent protein but not in Ad-AMPK-DN-infected myotubes. In Ad-AMPK-CA-transduced cells, serine phosphorylation of insulin receptor substrate 1 was decreased at a mammalian target of rapamycin (or p70 S6 kinase) target site that has been reported to be associated with insulin resistance. These data suggest that, in myotubes, activated AMPK[[alpha].sub.1] is sufficient to increase insulin action and that the presence of functional AMPK[alpha] is required for 5-aminoimidazole-4-carboxamide-1[beta],D-ribofuranoside-related increases in insulin action. compound C; AMPK; insulin sensitivity; Akt; mTOR

Data from the use of activators and inhibitors of the AMP-activated protein kinase (AMPK) suggest that AMPK increases sensitivity of glucose transport to stimulation by insulin in muscle ceils. We assayed insulin action after adenoviral (Ad) transduction of constitutively active (CA; a truncated form of AMPKα1) and dominant-negative (DN; which depletes endogenous AMPKα) forms of AMPKα (Ad-AMPKα-CA and Ad-AMPKα-DN, respectively) into C2C12 myotubes. Compared with control (Ad-green fluorescent protein), Ad-AMPK-CA increased the ability of insulin to stimulate glucose transport. The increased insulin action in cells expressing AMPK-CA was suppressed by compound C (an AMPK inhibitor). Exposure of cells to 5-aminoimidazole-4-carboxamide-1β-ᴅ-ribofuranoside (an AMPK activator) increased insulin action in uninfected myotubes and myotubes transduced with green fluorescent protein but not in Ad-AMPK-DN-infected myotubes. In Ad-AMPK-CA-transduced cells, serine phosphorylation of insulin receptor substrate 1 was decreased at a mammalian target of rapamycin (or p70 S6 kinase) target site that has been reported to be associated with insulin resistance. These data suggest that, in myotubes, activated AMPKα1 is sufficient to increase insulin action and that the presence of functional AMPKα is required for 5-aminoimidazole-4-carboxamide-1β,ᴅ-ribofuranoside-related increases in insulin action. [ABSTRACT FROM AUTHOR]

Introduction: Dexmedetomidine is a selective alpha-2 adrenoceptor agonist. It is conventionally used as a sedative in the intensive care unit. However, recently, the application of dexmedetomidine as an adjuvant to a local anesthetic agent has been studied. The present study intends to evaluate the effectiveness of dexmedetomidine as an adjuvant to 2% plain lignocaine for surgical removal of impacted mandibular third molar and to compare the efficacy of dexmedetomidine with 2% plain lignocaine with 2% lignocaine and 1:200000 adrenaline., Materials and Methods: A total of 80 patients who required surgical removal of impacted mandibular third molar extraction were included in the study. Patients were randomly divided into two groups using a computer-generated table. Patients in the study group received 2% plain lignocaine with 1 mcg/ml dexmedetomidine. Patients in the control group received 2% lignocaine with 1:200000 adrenaline. The parameters evaluated were onset and duration of action, pulse rate, blood pressure, oxygen saturation, and blood loss., Results: Onset of action was faster and the duration of action was longer when dexmedetomidine was used with lignocaine as a local anesthetic agent. The vital parameters in both the groups were stable. Bleeding at the surgical site was less in the dexmedetomidine group., Conclusion: The study concluded that the combination of dexmedetomidine with lignocaine enhances the local anesthetic potency of lignocaine when injected for nerve blocks., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 National Journal of Maxillofacial Surgery.)

Inflammation is often associated with the development and progression of cancer. The cells responsible for cancer-associated inflammation are genetically stable and thus are not subjected to rapid emergence of drug resistance; therefore, the targeting of inflammation represents an attractive strategy both for cancer prevention and for cancer therapy. Tumor-extrinsic inflammation is caused by many factors, including bacterial and viral infections, autoimmune diseases, obesity, tobacco smoking, asbestos exposure, and excessive alcohol consumption, all of which increase cancer risk and stimulate malignant progression. In contrast, cancer-intrinsic or cancer-elicited inflammation can be triggered by cancer-initiating mutations and can contribute to malignant progression through the recruitment and activation of inflammatory cells. Both extrinsic and intrinsic inflammations can result in immunosuppression, thereby providing a preferred background for tumor development. The current review provides a link between inflammation and cancer development., Competing Interests: None

Levodopa reportedly inhibits insulin action in skeletal muscle. Here we show that C2C12 myotubes produce levodopa and that insulin-stimulated glucose transport is enhanced when endogenous levodopa is depleted. Exogenous levodopa prevented the stimulation of glucose transport by insulin (P < 0.05) and increased cAMP concentrations (P < 0.05). The decrease in insulin-stimulated glucose transport caused by levodopa was attenuated by propranolol (a beta-adrenergic antagonist) and prevented by NSD-1015 (NSD), an inhibitor of DOPA decarboxylase (DDC; converts levodopa to dopamine). Propranolol and NSD both prevented levodopa-related increases in [cAMP]. However, the effects of levodopa were unlikely to be dependent on the conversion of levodopa to catecholamines because we could detect neither DDC in myotubes nor catecholamines in media after incubation of myotubes with levodopa. The data suggest the possibility of novel autocrine beta-adrenergic action in C2C12 myotubes in which levodopa, produced by myotubes, could have hormone-like effects that impinge on glucose metabolism.