Glucose utilization and disposal in cardiothoracic and skeletal muscles during the starved-to-fed transition in the rat.
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ABSTRACT:
SUBMITTER: Sugden MC
PROVIDER: S-EPMC1149667 | biostudies-other | 1990 Nov
REPOSITORIES: biostudies-other
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Project description:The progressive effects of starvation on muscle glucose utilization were studied in the conscious resting rat. High rates of glucose uptake and phosphorylation in constantly working cardiothoracic (heart, diaphragm) and postural skeletal muscles (soleus, adductor longus) were maintained for at least 9 h of starvation. A rapid decline in cardiac glucose utilization was observed during the period 9-24 h of starvation, but for the other muscles the decline was more gradual. Consequently, even after 24 h, rates of glucose utilization in these muscles remained quantitatively significant. In both cardiothoracic and working (postural) skeletal muscle, glucose uptake and phosphorylation and activity of the active form of pyruvate dehydrogenase exhibited differential sensitivities to starvation and also to acute elevation of fatty acid concentrations during acute (4-9 h) starvation, such that pyruvate oxidation was more rapidly suppressed than glucose uptake and phosphorylation. The results are discussed in relation to the role of the glucose/fatty acid cycle in glucose conservation during the fed-to-starved transition.
| S-EPMC1131705 | biostudies-other
Project description:The pattern of glycogen deposition in skeletal muscles of varying fibre composition was examined in rats during the starved-to-fed transition. In all the muscles studied, glycogen concentrations steadily increased during the first 8 h after chow re-feeding, and the fed value was exceeded. Rates of glycogen deposition varied, not with muscle fibre composition, but with the extent of glycogen depletion during starvation. There was no evidence for skeletal-muscle glycogen breakdown during the period of hepatic glycogenesis, making it unlikely that recycling of carbon from muscle glycogen to lactate is quantitatively important for the provision of glycogenic precursors to the liver, but moderate glycogen loss was observed from 8 to 24 h after re-feeding, when the liver is in the lipogenic mode. The factors influencing glucose disposal by skeletal muscle after re-feeding are discussed.
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Project description:Glucose utilization indices (GUI) were measured in vivo in conjunction with active pyruvate dehydrogenase complex (PDH(a) and glycogen synthase (GS) activities in fast-twitch skeletal muscles [extensor digitorum longus (EDL), tibialis anterior and gastrocnemius] of late-pregnant rats and age-matched virgin control rats in the fed state, after 24 h starvation and at 2 h after re-feeding with standard laboratory chow ad libitum after 24 h starvation. As demonstrated previously [Holness and Sugden (1990) Biochem. J 277, 429-433], GUI values of fast-twitch skeletal muscles of virgin rats were low in the fed ad libitum and the 24 h-starved states, but dramatically increased after subsequent chow re-feeding. GUI values of fast-twitch skeletal muscles of late-pregnant rats were also low in the fed and starved states and were increased by re-feeding, but the increase in GUI values elicited by re-feeding was greatly attenuated. PDHa activities in EDL, tibialis anterior and gastrocnemius in the fed state were unaffected by late pregnancy, and skeletal-muscle PDHa activities were decreased after 24 h of starvation in both groups. Whereas re-feeding of virgin rats with standard diet for 2 h restored PDHa activities in fast-twitch skeletal muscles to values for rats continuously fed ad libitum, PDHa activities in fast-twitch skeletal muscles of late-pregnant rats, although increased in response to re-feeding, remained considerably less than the corresponding fed ad libitum values after 2 h of re-feeding. In contrast, neither skeletal-muscle GS re-activation nor rates of skeletal-muscle glycogen deposition after re-feeding were markedly affected by late pregnancy. The results are discussed in relation to the specific targeting of individual pathways of glucose disposal in fast-twitch skeletal muscles during re-feeding in late pregnancy.
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Project description:In the fed state, hyperthyroidism increased glucose utilization indices (GUIs) of skeletal muscles containing a lower proportion of oxidative fibres. Glycogen concentrations were unchanged, but active pyruvate dehydrogenase (PDHa) activities were decreased. Hyperthyroidism attenuated the effects of 48 h of starvation to decrease muscle GUI. Glycogen concentrations and PDHa activities after 48 h of starvation were low and similar in euthyroid and hyperthyroid rats. The increase in glucose uptake and phosphorylation relative to oxidation and storage in skeletal muscle induced by hyperthyroidism may contribute to increased glucose re-cycling in the fed hyperthyroid state and to glucose turnover in the starved hyperthyroid state.
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Project description:Arteriovenous glucose difference across the mammary gland of the lactating rat was used as an 'instantaneous' monitor of mammary glucose uptake. Plasma [glucose] and arteriovenous glucose difference varied according to whether Halothane, diethyl ether or sodium pentobarbitone anaesthesia was used. In pentobarbitone-treated rats a 60% glucose extraction in the fed state decreased to 5% after 18 h starvation, and recovered to 40% and 59% after 15 min and 60 min re-feeding respectively. The increase and decrease in plasma [fatty acids] and the depletion and restoration of hepatic glycogen mostly followed similar time courses. Re-feeding was accompanied by a brief surge of plasma [insulin]. Starved lactating rats showed a markedly greater capacity than age-matched virgin rats in the oral and intraperitoneal glucose tolerance tests. Mammary glucose uptake in the starved rat was significantly restored by oral or intraperitoneal glucose or by insulin, but not by acetoacetate or by heparin-induced elevation of plasma [fatty acids]. The role of insulin and of possible changes in mammary sensitivity to insulin in the return of mammary glucose uptake on re-feeding is discussed.
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Project description:Muscle stem cells (MuSCs) are involved in homeostatic maintenance of skeletal muscle and play a central role in muscle regeneration in response to injury. Thus, understanding MuSC autonomous properties is of fundamental importance for studies of muscle degenerative diseases and muscle plasticity. Rat, as an animal model, has been widely used in the skeletal muscle field, however rat MuSC isolation through fluorescence-activated cell sorting has never been described. This work validates a protocol for effective MuSC isolation from rat skeletal muscles. Tibialis anterior was harvested from female rats and digested for isolation of MuSCs. Three protocols, employing different cell surface markers (CD106, CD56, and CD29), were compared for their ability to isolate a highly enriched MuSC population. Cells isolated using only CD106 as a positive marker showed high expression of Pax7, ability to progress through myogenic lineage while in culture, and complete differentiation in serum-deprived conditions. The protocol was further validated in gastrocnemius, diaphragm, and the individual components of the pelvic floor muscle complex (coccygeus, iliocaudalis, and pubocaudalis), proving to be reproducible. CD106 is an efficient marker for reliable isolation of MuSCs from a variety of rat skeletal muscles.
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Project description:OBJECTIVE:WWOX, a well-established tumor suppressor, is frequently lost in cancer and plays important roles in DNA damage response and cellular metabolism. METHODS:We re-analyzed several genome-wide association studies (GWAS) using the Type 2 Diabetes Knowledge Portal website to uncover WWOX's association with metabolic syndrome (MetS). Using several engineered mouse models, we studied the effect of somatic WWOX loss on glucose homeostasis. RESULTS:Several WWOX variants were found to be strongly associated with MetS disorders. In mouse models, somatic ablation of Wwox in skeletal muscle (Wwox?SKM) results in weight gain, glucose intolerance, and insulin resistance. Furthermore, Wwox?SKM mice display reduced amounts of slow-twitch fibers, decreased mitochondrial quantity and activity, and lower glucose oxidation levels. Mechanistically, we found that WWOX physically interacts with the cellular energy sensor AMP-activated protein kinase (AMPK) and that its loss is associated with impaired activation of AMPK, and with significant accumulation of the hypoxia inducible factor 1 alpha (HIF1?) in SKM. CONCLUSIONS:Our studies uncover an unforeseen role of the tumor suppressor WWOX in whole-body glucose homeostasis and highlight the intimate relationship between cancer progression and metabolic disorders, particularly obesity and type-2 diabetes. SUBJECT AREAS:Genetics, Metabolic Syndrome, Diabetes.
| S-EPMC6437662 | biostudies-literature
Project description:We measured glucose utilization index (GUI) values in individual skeletal muscles of conscious rats during the light (quiescent) and dark (feeding/activity) phases. There was a 2-3-fold variation in muscle GUI values, with peak values observed at the end of the dark phase and minimum values observed at 6-9 h into the light phase. GUI values in working muscles (soleus and adductor longus) were consistently higher than in non-working muscles (tibialis anterior and extensor digitorum longus), indicating that working muscles make the major contribution of the total skeletal muscle mass to glucose disposal during unrestricted feeding. There was a clear overall increase in muscle glycogen deposition during the first 9 h of the dark phase; this was concomitant with an increase in food consumption. Peak glycogen concentrations were reached after 9 h of darkness, but subsequently declined. The pattern of changes in muscle GUI values during the light and dark phases is discussed in relation to the role of insulin in facilitating glucose clearance.
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Project description:Bromocriptine mesylate treatment was examined in dogs fed a high fat diet (HFD) for 8 wk. After 4 wk on HFD, daily bromocriptine (Bromo; n = 6) or vehicle (CTR; n = 5) injections were administered. Oral glucose tolerance tests were performed before beginning HFD (OGTT1), 4 wk after HFD began (Bromo only), and after 7.5 wk on HFD (OGTT3). After 8 wk on HFD, clamp studies were performed, with infusion of somatostatin and intraportal replacement of insulin (4× basal) and glucagon (basal). From 0 to 90 min (P1), glucose was infused via peripheral vein to double the hepatic glucose load; and from 90 to 180 min (P2), glucose was infused via the hepatic portal vein at 4 mg·kg-1·min-1, with the HGL maintained at 2× basal. Bromo decreased the OGTT glucose ΔAUC0-30 and ΔAUC0-120 by 62 and 27%, respectively, P < 0.05 for both) without significantly altering the insulin response. Bromo dogs exhibited enhanced net hepatic glucose uptake (NHGU) compared with CTR (~33 and 21% greater, P1 and P2, respectively, P < 0.05). Nonhepatic glucose uptake (non-HGU) was increased ~38% in Bromo in P2 (P < 0.05). Bromo vs. CTR had higher (P < 0.05) rates of glucose infusion (36 and 30%) and non-HGU (~40 and 27%) than CTR during P1 and P2, respectively. In Bromo vs. CTR, hepatic 18:0/16:0 and 16:1/16:0 ratios tended to be elevated in triglycerides and were higher (P < 0.05) in phospholipids, consistent with a beneficial effect of bromocriptine on liver fat accumulation. Thus, bromocriptine treatment improved glucose disposal in a glucose-intolerant model, enhancing both NHGU and non-HGU.
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Project description:Insulin resistance (IR) in skeletal muscle is a prerequisite for type 2 diabetes and is often associated with obesity. IR also develops alongside muscle atrophy in older individuals in sarcopenic obesity. The molecular defects that underpin this syndrome are not well characterized, and there is no licensed treatment. Deletion of the transforming growth factor-β family member myostatin, or sequestration of the active peptide by overexpression of the myostatin propeptide/latency-associated peptide (ProMyo) results in both muscle hypertrophy and reduced obesity and IR. We aimed to establish whether local myostatin inhibition would have a paracrine/autocrine effect to enhance glucose disposal beyond that simply generated by increased muscle mass, and the mechanisms involved. We directly injected adeno-associated virus expressing ProMyo in right tibialis cranialis/extensor digitorum longus muscles of rats and saline in left muscles and compared the effects after 17 days. Both test muscles were increased in size (by 7 and 11%) and showed increased radiolabeled 2-deoxyglucose uptake (26 and 47%) and glycogen storage (28 and 41%) per unit mass during an intraperitoneal glucose tolerance test. This was likely mediated through increased membrane protein levels of GLUT1 (19% higher) and GLUT4 (63% higher). Interestingly, phosphorylation of phosphoinositol 3-kinase signaling intermediates and AMP-activated kinase was slightly decreased, possibly because of reduced expression of insulin-like growth factor-I in these muscles. Thus, myostatin inhibition has direct effects to enhance glucose disposal in muscle beyond that expected of hypertrophy alone, and this approach may offer potential for the therapy of IR syndromes.
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