Peripheral Glucose Metabolism in Acromegaly

Foss, Milton César; Saad, Mário J.A.; Paccola, G M G F; Paula, Francisco José Albuquerque de; Piccinato, Carlos Eli; Moreira, Ayrton Custódio

doi:10.1210/jcem-72-5-1048

Cited by 82 publications

(59 citation statements)

References 27 publications

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“…Furthermore, abnormal GH secretion in acromegalic patients lead to impaired intravenous and oral glucose disposal that is associated with hyperinsulinemia (42-46), impaired insulin-stimulated glucose uptake, and impaired suppression of hepatic glucose production during hyperinsulinemic-euglycemic clamping (47). It has also been shown that treatment of acromegalic patients with exogenous insulin did not improve muscle glucose uptake or decrease hepatic glucose output (48,49). Thus, increased insulin secretion in those patients does not compensate for the increased insulin resistance, which is believed to be mediated through the GHR (50).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of growth hormone action improves insulin sensitivity in liver IGF-1–deficient mice

et al. 2004

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Liver IGF-1-deficient (LID) mice have a 75% reduction in circulating IGF-1 levels and, as a result, a fourfold increase in growth hormone (GH) secretion. To block GH action, LID mice were crossed with GH antagonist (GHa) transgenic mice. Inactivation of GH action in the resulting LID + GHa mice led to decreased blood glucose and insulin levels and improved peripheral insulin sensitivity. Hyperinsulinemic-euglycemic clamp studies showed that LID mice exhibit severe insulin resistance. In contrast, expression of the GH antagonist transgene in LID + GHa mice led to enhanced insulin sensitivity and increased insulin-stimulated glucose uptake in muscle and white adipose tissue. Interestingly, LID + GHa mice exhibit a twofold increase in white adipose tissue mass, as well as increased levels of serumfree fatty acids and triglycerides, but no increase in the triglyceride content of liver and muscle. In conclusion, these results show that despite low levels of circulating IGF-1, insulin sensitivity in LID mice could be improved by inactivating GH action, suggesting that chronic elevation of GH levels plays a major role in insulin resistance. These results suggest that IGF-1 plays a role in maintaining a fine balance between GH and insulin to promote normal carbohydrate and lipid metabolism.

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Section: Discussionmentioning

confidence: 99%

Inhibition of growth hormone action improves insulin sensitivity in liver IGF-1–deficient mice

et al. 2004

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“…Because glucocorticoids and GH have similar effects on lipolysis (24) and insulin sensitivity (43,44), it is likely that the high corticosterone levels in both Mt-bGH and GFAP-bGH mice contribute to the insulin resistance observed in both animal models.…”

Section: Discussionmentioning

confidence: 99%

“…These are known effects of GH (3,(42)(43)(44), but the importance of GH production in the CNS for these effects in an animal model that is not GH deficient is not known.…”

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confidence: 99%

Growth Hormone Overexpression in the Central Nervous System Results in Hyperphagia-Induced Obesity Associated With Insulin Resistance and Dyslipidemia

et al. 2005

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It is well known that peripherally administered growth hormone (GH) results in decreased body fat mass. However, GH-deficient patients increase their food intake when substituted with GH, suggesting that GH also has an appetite stimulating effect. Transgenic mice with an overexpression of bovine GH in the central nervous system (CNS) were created to investigate the role of GH in CNS. This study shows that overexpression of GH in the CNS differentiates the effect of GH on body fat mass from that on appetite. The transgenic mice were not GH-deficient but were obese and showed increased food intake as well as increased hypothalamic expression of agouti-related protein and neuropeptide Y. GH also had an acute effect on food intake following intracerebroventricular injection of C57BL/6 mice. The transgenic mice were severely hyperinsulinemic and showed a marked hyperplasia of the islets of Langerhans. In addition, the transgenic mice displayed alterations in serum lipid and lipoprotein levels and hepatic gene expression. In conclusion, GH overexpression in the CNS results in hyperphagia-induced obesity indicating a dual effect of GH with a central stimulation of appetite and a peripheral lipolytic effect. Diabetes 54:51-62, 2005

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“…Premature death is mainly due to a specific cardiomyopathy (4) worsened by the coexistence of several cardiovascular risk factors, such as abnormal carbohydrate metabolism and/or insulin resistance (5,6). The objectives of treatment include normalization of GH/IGF-I secretion and control of pituitary tumor growth and acromegalyrelated comorbidities in order to normalize quality of life and mortality (7).…”

Section: Introductionmentioning

confidence: 99%

Preliminary data on biochemical remission of acromegaly after somatostatin analogs withdrawal

Ronchi

Rizzo

Lania

et al. 2008

European Journal of Endocrinology

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Objective: It is still unknown whether prolonged treatment with somatostatin analogs (SSTa) may cause a long-lasting disease remission in GH-secreting adenomas after drug discontinuation. The aim of the present study was to investigate the evolution of GH/IGF-I secretion and tumor mass after SSTa withdrawal in patients affected by acromegaly. Patients and Design: A total of 27 patients with acromegaly (12 de novo and 15 previously operated) were treated with SSTa for a median period of 48 months and considered optimally controlled in hormonal and neuroradiological terms. None of them were previously irradiated. Methods: Basal GH, post-glucose GH nadir, IGF-I, clinical signs/symptoms, and metabolic parameters were evaluated after 12-16 weeks from drug withdrawal. Only patients who met the current criteria for disease remission remained in drug suspension being periodically re-evaluated for biochemical/-clinical data and neuroradiological imaging. Results: After 12-16 weeks withdrawal, 15 of the 27 patients had disease relapse and restarted SSTa, while 12 were considered 'in disease remission' (44% of total). Glucose metabolism improved in both euglycemic and diabetic patients after short-term SSTa discontinuation. Only one of the ten patients who reached 24 weeks withdrawal showed biochemical disease recurrence. On the whole, five of the patients still in remission after 6 months have already prolonged the follow-up over 12 months (median: 24 months), without clinical and biochemical/neuroradiological evidence of disease recurrence. Conclusions: These preliminary data indicate a successful withdrawal of SSTa at least in a subset of wellresponsive patients with acromegaly and challenge the previously held concept that medical therapy is always a lifelong requirement.

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Peripheral Glucose Metabolism in Acromegaly

Cited by 82 publications

References 27 publications

Inhibition of growth hormone action improves insulin sensitivity in liver IGF-1–deficient mice

Inhibition of growth hormone action improves insulin sensitivity in liver IGF-1–deficient mice

Growth Hormone Overexpression in the Central Nervous System Results in Hyperphagia-Induced Obesity Associated With Insulin Resistance and Dyslipidemia

Preliminary data on biochemical remission of acromegaly after somatostatin analogs withdrawal

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