Insulin action and hepatic glucose cycling in Cushing's syndrome

Heaney, April; Harper, Ray; Ennis, C. N.; Rooney, D. P.; Sheridan, B.; Atkinson, A. B.; Bell, P. M.

doi:10.1046/j.1365-2265.1997.2121024.x

Cited by 17 publications

(16 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It should be considered that, within an insulin-resistant state scenario, we were able to determine that, in chronic hypercorticosteronemic MSG rats, similarly to that previously found in Cushing's patients [47], the liver high activity of the two key enzymes, GCK and G6Pase, assures (within a very active futile cycle) a drastic increase of high glucose liver content. Although a previous study has reported an enhanced activity of G6Pase in MSG animals [48], to our knowledge this is the first report of an active involvement of GCK, the hepatic glucose sensor, in the changes induced by MSG.…”

Section: Discussionsupporting

confidence: 68%

Chronic Glucocorticoid-Rich Milieu and Liver Dysfunction

Villagarcía

Sabugo

Castro

et al. 2016

International Journal of Endocrinology

View full text Add to dashboard Cite

We investigated the impact of chronic hypercorticosteronemia (due to neonatal monosodium L-glutamate, MSG, and treatment) on liver oxidative stress (OS), inflammation, and carbohydrate/lipid metabolism in adult male rats. We evaluated the peripheral concentrations of several metabolic and OS markers and insulin resistance indexes. In liver we assessed (a) OS (GSH and protein carbonyl groups) and inflammatory (IL-1b, TNFa, and PAI-1) biomarkers and (b) carbohydrate and lipid metabolisms. MSG rats displayed degenerated optic nerves, hypophagia, low body and liver weights, and enlarged adipose tissue mass; higher peripheral levels of glucose, triglycerides, insulin, uric acid, leptin, corticosterone, transaminases and TBARS, and peripheral and liver insulin resistance; elevated liver OS, inflammation markers, and glucokinase (mRNA/activity) and fructokinase (mRNA). Additionally, MSG liver phosphofructokinase-2, glucose-6-phosphatase (mRNA and activity) and glucose-6-phosphate dehydrogenase, Chrebp, Srebp1c, fatty acid synthase, and glycerol-3-phosphate (mRNAs) were increased. In conclusion adult MSG rats developed an insulin-resistant state and increased OS and serious hepatic dysfunction characterized by inflammation and metabolic signs suggesting increased lipogenesis. These features, shared by both metabolic and Cushing's syndrome human phenotypes, support that a chronic glucocorticoid-rich endogenous environment mainly impacts on hepatic glucose cycle, displacing local metabolism to lipogenesis. Whether correcting the glucocorticoid-rich environment ameliorates such dysfunctions requires further investigation.

show abstract

Section: Discussionsupporting

confidence: 68%

Chronic Glucocorticoid-Rich Milieu and Liver Dysfunction

Villagarcía

Sabugo

Castro

et al. 2016

International Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…GCA during early lactation ranged from 0 to 15% of glucose production. This is very similar to GCA rates of other species studied (34,40,61,75,78). Previous studies are conflicting on the glucose cycle's response to alterations in hormone levels.…”

Section: Discussionsupporting

confidence: 83%

Glucose metabolism during lactation in a fasting animal, the northern elephant seal

Champagne¹,

Houser²,

Crocker³

2006

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

Fasting is associated with a series of physiological responses that protect body tissues from degradation by efficiently using expendable energy reserves while sparing protein. Lactation requires the mobilization of maternal nutrients for milk synthesis. The rare life history trait of fasting simultaneous with lactation results in the conflicting demands of provisioning offspring while meeting maternal metabolic costs and preserving maternal tissues for her own survival and future reproduction. Certain tissues continue to require glucose for operation during fasting and might constrain tissue mobilization for lactogenesis due to a need for gluconeogenic substrates. This study investigated glucose flux, glucose cycle activity, and the influence of regulatory hormones in fasting lactating northern elephant seals. Measurements were taken early (5 days) and late (21 days) during the lactation period and, as a nonlactating comparison, after the completion of molting. Glucose cycle activity was highly variable in all study groups and did not change over lactation (P > 0.3), whereas endogenous glucose production decreased during lactation (t = -3.41, P = 0.008). Insulin and insulin-to-glucagon molar ratio decreased across lactation (t = 6.48, 4.28; P = 0.0001, 0.002), while plasma cortisol level increased (t = 4.15, P = 0.002). There were no relationships between glucose production and hormone levels. The glucose production values measured exceeded that predicted from available gluconeogenic substrate, indicating substantial glucose recycling in this species.

show abstract

“…Variation in proportional glucose cycle activity was high between individuals, but taken as a whole, the proportion was nearly consistent between early and late fasting periods. Values of pGCA found in this study are similar to those reported in other species measured: 12.6% in postabsorptive dog (Issekutz, 1977) and from 11-25% in postabsorptive humans (Shulman et al, 1985;Neely et al, 1992;Rooney et al, 1992;Heaney et al, 1997). There is no evidence to suggest that the glucose cycle varies the regulation of glucose availability across the fast; rather, it changes in parallel with EGP.…”

Section: The Journal Of Experimental Biologysupporting

confidence: 76%

Glucose production and substrate cycle activity in a fasting adapted animal, the northern elephant seal

Champagne

Houser

Crocker

2005

Journal of Experimental Biology

View full text Add to dashboard Cite

During prolonged fasting physiological mechanisms defend lean tissue from catabolism. In the fasting state, glucose is derived solely from gluconeogenesis, requiring some catabolism of amino acids for gluconeogenic substrates. This creates a conflict in animals undergoing fasts concurrently with metabolically challenging activities. This study investigated glucose metabolism in fasting and developing neonatal elephant seals. Glucose production and glucose cycle activity were measured early (2 weeks) and late (6 weeks) in the postweaning fasting period. Additionally the role of regulatory hormones on glucose production and glucose cycle activity were investigated. Glucose cycle activity was highly variable throughout the study period, did not change over the fasting period, and was not correlated with insulin or glucagon level. Endogenous glucose production (EGP) was 2.80±0.65·mg·kg -1 ·min -1 early and 2.21±0.12 during late fasting. Insulin to glucagon molar ratio decreased while cortisol levels increased over the fast (t=5.27, 2.84; P=0.003, 0.04; respectively). There was no relationship between EGP and hormone levels. The glucose production values measured in this study were high and exceeded the estimated gluconeogenic substrate available. These data suggest extensive glucose recycling via Cori cycle activity occurring in northern elephant seals, and we propose a possible justification for this recycling.

show abstract

Insulin action and hepatic glucose cycling in Cushing's syndrome

Cited by 17 publications

References 0 publications

Chronic Glucocorticoid-Rich Milieu and Liver Dysfunction

Chronic Glucocorticoid-Rich Milieu and Liver Dysfunction

Glucose metabolism during lactation in a fasting animal, the northern elephant seal

Glucose production and substrate cycle activity in a fasting adapted animal, the northern elephant seal

Contact Info

Product

Resources

About