ABSTRACT
We have investigated the activation of the extracellular signal-regulated kinases (ERK1 and ERK2) by muscle contraction and insulin in perfused rat skeletal muscle. Both stimuli activated ERK1 and ERK2 by an upstream kinase MAP/ERK kinase (MEK)-dependent mechanism, as the MEK inhibitor PD-98059 inhibited ERK phosphorylation. The presence of the phosphatidylinositol (PI) 3-kinase inhibitors LY-294002 and wortmannin totally eradicated ERK1 and ERK2 phosphorylation in response to insulin but not contraction. Insulin and muscle contraction activated muscle glucose transport, glycogen synthase, and amino acid transport independently of ERK signaling, whereas the PI 3-kinase inhibitors abolished the stimulatory effects of insulin but not those of contraction on these three cellular processes. We conclude that 1) insulin and contraction activate ERK signaling in skeletal muscle; 2) ERK signaling is not necessary for activation of glucose and amino acid transport or glycogen synthase activity by contraction and insulin in skeletal muscle; and 3) insulin-induced activation of MEK, the upstream activator of ERK, is dependent on PI 3-kinase, whereas contraction utilizes a different mechanism.
Subject(s)
Insulin/pharmacology , Mitogen-Activated Protein Kinases/metabolism , Muscle Contraction/physiology , Muscle, Skeletal/enzymology , Amino Acids/metabolism , Androstadienes/pharmacology , Animals , Chromones/pharmacology , Enzyme Inhibitors/pharmacology , Flavonoids/pharmacology , Glucose/metabolism , Glycogen Synthase/metabolism , Male , Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors , Morpholines/pharmacology , Muscle, Skeletal/drug effects , Phosphoinositide-3 Kinase Inhibitors , Phosphorylation/drug effects , Rats , Rats, Wistar , Signal Transduction/physiology , WortmanninABSTRACT
It has been postulated that the perfused rat hindlimb is unsuitable for measurements of muscle glucose transport [P. Hansen, E. Gulve, J. Gao, J. Schluter, M. Mueckler, and J. Holloszy. Am. J. Physiol. 268 (Cell Physiol. 37): C30-C35, 1995]. The aim of the present study was therefore to critically evaluate the suitability of this preparation for glucose transport measurements using the extracellular marker mannitol and the glucose analogs 3-O-methyl-D-glucose or 2-deoxy-D-glucose. In all three muscle fiber types studied, the rate of 2-deoxy-D-glucose uptake during perfusion was linear from 1 to 40 min during maximal insulin stimulation and from 1 to 15 min during maximal electrical stimulation. Uptake of 2-deoxy-D-glucose was not increased by an increase in perfusate flow. Combined stimulation with a maximal insulin concentration and electrical stimulation elicited additive effects on 2-deoxy-D-glucose uptake in slow- and fast-twitch oxidative but not in fast-twitch glycolytic muscle fibers. Furthermore, in muscles having high glucose transport capacities 3-O-methyl-D-glucose is less suitable than 2-deoxy-D-glucose because of rapidly developing nonlinearity of accumulation. Our findings clearly demonstrate that the perfused hindlimb is suitable for measurements of muscle glucose transport and that the most feasible glucose analog for this purpose is 2-deoxy-D-glucose.
Subject(s)
Glucose/metabolism , Insulin/pharmacology , Muscle Contraction/physiology , Muscle Fibers, Fast-Twitch/physiology , Muscle, Skeletal/physiology , 3-O-Methylglucose/metabolism , Analysis of Variance , Animals , Biological Transport , Deoxyglucose/metabolism , Electric Stimulation , Hindlimb , Kinetics , Mannitol/pharmacokinetics , Muscle Fibers, Fast-Twitch/drug effects , Muscle, Skeletal/blood supply , Muscle, Skeletal/drug effects , Perfusion/methods , RatsABSTRACT
In 1986 The National Board of Health published guidelines for cervical cancer screening in Denmark. These guidelines recommend organized screening with personal invitations every three years to women in the age group 23-59 years, and in the years to come also invitation of women aged 60-74 years. We studied the organization of cervical cancer screening in Danish counties at the beginning of 1994. Organized screening programmes are running in 15 out of the 16 "counties" (this include the municipalities of København and Frederiksberg). Four counties completely follow the national guidelines. Eight counties follow these guidelines in general, but they do not invite women above the age of 60 years. In total, 72% of women aged 25-74 years are at present invited for cervical cancer screening in Denmark.
Subject(s)
Mass Screening/trends , Uterine Cervical Neoplasms/prevention & control , Adult , Aged , Denmark , Female , Humans , Mass Screening/organization & administration , Middle Aged , Vaginal SmearsABSTRACT
In a prospective study, 86 women who had an IUD (Nova-T) inserted immediately after induced abortion were compared to 95 abortion patients who started another contraception (control I). Additionally, the rate of complications following IUD insertion in a Family Planning Clinic (control II) were studied in 83 non-pregnant women. The overall infection rate for post-abortion patients was 4.4% (5.8% in the study group, 3.2% in control I). No infections were observed in control group II. Confidence limits (95%) for the three groups were overlapping. Among the women in the study group, bleeding and pain were not more frequent, but if one of these complications occurred, it tended to be more serious and the duration was longer. The number of days before resumption of work after abortion was 3-4 days in both abortion groups. After three months, the continuation rate was 83% (71 of 86) in the study group, 76% (72 of 95) in control I and 93% (77 of 83) in control II. Sixty-nine of the 181 women admitted for legal abortion had been admitted for the same reason previously. In this study, the recurrence rate after 12 months was 0% in the study group and 4.2% (4 of 95) in control group I. The insertion of an IUD at the time of abortion seems to be an effective and acceptable solution to the problem of recurrent abortion.
