Association between diencephalic thyroliberin and arterial blood pressure in agouti-yellow and ob/ob mice may be mediated by leptin

Burgueño, Adriana Laura; Landa, María Silvina; Schuman, Mariano Luis; Alvarez, Azucena L.; Carabelli, Julieta; Garcı́a, Silvia; Pirola, Carlos José

doi:10.1016/j.metabol.2007.06.008

Cited by 12 publications

(5 citation statements)

References 32 publications

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“…Notably, the TRH1 knockout mouse has a prolonged sleep time with pentobarbital (Thirunarayanan et al, 2013). Similarly, the obese leptin knockout mouse (ob/ob) and the Brown Norway rat are TRH deficient in certain neuronal populations (Burgueno et al, 2007;Puissant et al, 2015). Of note, the ob/ ob mouse has disordered ventilation at baseline and the Brown Norway rat lacks a hypercarbic ventilatory response (O'Donnell et al, 1999;Puissant et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

“…interesting to determine if there are differences in the breathing effects of intravenous TRH relative to agents that increase endogenous TRH levels through blockade of TRH proteolysis (Scalabrino et al, 2007), or following leptin administration, which induces endogenous TRH expression (Burgueno et al, 2007) and gates TRH responsivity (Rogers et al, 2009). Finally, benzodiazepines (e.g., chlordiazepoxide and midazolam) are antagonists/inverse agonists of the TRH receptor and antagonize some physiologic responses to TRH administration (e.g., TSH and prolactin secretion) (Roussel et al, 1986;Lu et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

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Intravenous and Intratracheal Thyrotropin Releasing Hormone and Its Analog Taltirelin Reverse Opioid-Induced Respiratory Depression in Isoflurane Anesthetized Rats

Boghosian

Luethy

Cotten

2018

J Pharmacol Exp Ther

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Thyrotropin releasing hormone (TRH) is a tripeptide hormone and a neurotransmitter widely expressed in the central nervous system that regulates thyroid function and maintains physiologic homeostasis. Following injection in rodents, TRH has multiple effects including increased blood pressure and breathing. We tested the hypothesis that TRH and its long-acting analog, taltirelin, will reverse morphine-induced respiratory depression in anesthetized rats following intravenous or intratracheal (IT) administration. TRH (1 mg/kg plus 5 mg/kg/h, i.v.) and talitrelin (1 mg/kg, i.v.), when administered to rats pretreated with morphine (5 mg/kg, i.v.), increased ventilation from 50% ± 6% to 131% ± 7% and 45% ± 6% to 168% ± 13%, respectively (percent baseline; = 4 ± S.E.M.), primarily through increased breathing rates (from 76% ± 9% to 260% ± 14% and 66% ± 8% to 318% ± 37%, respectively). By arterial blood gas analysis, morphine caused a hypoxemic respiratory acidosis with decreased oxygen and increased carbon dioxide pressures. TRH decreased morphine effects on arterial carbon dioxide pressure, but failed to impact oxygenation; taltirelin reversed morphine effects on both arterial carbon dioxide and oxygen. Both TRH and talirelin increased mean arterial blood pressure in morphine-treated rats (from 68% ± 5% to 126% ± 12% and 64% ± 7% to 116% ± 8%, respectively; = 3 to 4). TRH, when initiated prior to morphine (15 mg/kg, i.v.), prevented morphine-induced changes in ventilation; and TRH (2 mg/kg, i.v.) rescued all four rats treated with a lethal dose of morphine (5 mg/kg/min, until apnea). Similar to intravenous administration, both TRH (5 mg/kg, IT) and taltirelin (2 mg/kg, IT) reversed morphine effects on ventilation. TRH or taltirelin may have clinical utility as an intravenous or inhaled agent to antagonize opioid-induced cardiorespiratory depression.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Intravenous and Intratracheal Thyrotropin Releasing Hormone and Its Analog Taltirelin Reverse Opioid-Induced Respiratory Depression in Isoflurane Anesthetized Rats

Boghosian

Luethy

Cotten

2018

J Pharmacol Exp Ther

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“…In fact, BTBR ob/ob mice are hypotensive compared with BTBR WT and heterozygous controls (Supplemental Figure 5), likely a direct consequence of leptin deficiency. 16,17 Podocyte Number and Density…”

Section: Renal Structural Alterationsmentioning

confidence: 99%

BTBR Ob/Ob Mutant Mice Model Progressive Diabetic Nephropathy

Hudkins

Pichaiwong

Wietecha

et al. 2010

Journal of the American Society of Nephrology

204

284

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There remains a need for robust mouse models of diabetic nephropathy (DN) that mimic key features of advanced human DN. The recently developed mouse strain BTBR with the ob/ob leptin-deficiency mutation develops severe type 2 diabetes, hypercholesterolemia, elevated triglycerides, and insulin resistance, but the renal phenotype has not been characterized. Here, we show that these obese, diabetic mice rapidly develop morphologic renal lesions characteristic of both early and advanced human DN. BTBR ob/ob mice developed progressive proteinuria beginning at 4 weeks. Glomerular hypertrophy and accumulation of mesangial matrix, characteristic of early DN, were present by 8 weeks, and glomerular lesions similar to those of advanced human DN were present by 20 weeks. By 22 weeks, we observed an approximately 20% increase in basement membrane thickness and a Ͼ50% increase in mesangial matrix. Diffuse mesangial sclerosis (focally approaching nodular glomerulosclerosis), focal arteriolar hyalinosis, mesangiolysis, and focal mild interstitial fibrosis were present. Loss of podocytes was present early and persisted. In summary, BTBR ob/ob mice develop a constellation of abnormalities that closely resemble advanced human DN more rapidly than most other murine models, making this strain particularly attractive for testing therapeutic interventions. Diabetic nephropathy (DN) is the largest single cause of ESRD in the United States, accounting for nearly half of the patients who enter the dialysis patient population each year and currently accounting for 45% of prevalent kidney failure in the United States. 1-4 Although both type 1 and type 2 diabetes lead to DN, the current epidemic of DN is due to type 2 diabetes; however, understanding the mechanisms that produce the constellation of clinical and pathologic alterations that define DN in humans remains very incomplete, in part because clinical DN is a slowly progressive disease, and relevant animal models that produce this constellation of pathologic and clinical abnormalities have important limitations. Mice rendered hyperglycemic by administration of streptozotocin (STZ) or through genetic predisposition such as the db/db mouse can develop some features of DN, most notably glomerular mesangial expansion, but do so only over prolonged periods and do not progress to ESRD. [5][6][7][8][9] Most murine models to date have failed to develop reliably marked mesangial expansion or the

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“…6), presumably due to a persistent hyperglycemia and glucose toxicity. B6J-A y mice are hypertensive compared to C57BL/6J-Lep ob (B6J-ob) mice that show similarly pronounced obesity [27,28]. Further comprehensive analyses of pathophysiology of pancreas and kidney, including complications caused by persistent hyperglycemia, are needed in NSY.B6-Tyr + ,A y mice.…”

Section: Discussionmentioning

confidence: 99%

A novel model mouse for type 2 diabetes mellitus with early onset and persistent hyperglycemia

et al. 2022

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Various mouse models of type 2 diabetes have been established, but few of these show early onset and persistent hyperglycemia. We have established a congenic mouse strain (NSY.B6-Tyr + ,A y ) in which a spontaneous mutation of the agouti yellow (A y ) gene, which causes obesity by hyperphagia, was introduced into the NSY strain, which shows increased glucose intolerance with age. This strain has been maintained as a segregating inbred strain by mating obese yellow (A y /a) males with normal black (a/a) females. All yellow males showed marked obesity and hyperglycemia (mean blood glucose level >400 mg/dl) from 10 to 24 weeks of age. The yellow males also showed glucose intolerance and insulin resistance. They provide a potentially valuable model mouse for research into type 2 diabetes, hyperlipidemia, fatty liver, and renal glomerular complications. Yellow female mice also showed marked obesity, but the incidence of diabetes and the severity of various pathological conditions were milder than in yellow males. None of the black mice showed hyperglycemia in either sex. NSY.B6-Tyr + ,A y strain has good fertility and does not display inter-male aggression, making them useful as a new model for type 2 diabetes with early onset and persistent hyperglycemia.

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Association between diencephalic thyroliberin and arterial blood pressure in agouti-yellow and ob/ob mice may be mediated by leptin

Cited by 12 publications

References 32 publications

Intravenous and Intratracheal Thyrotropin Releasing Hormone and Its Analog Taltirelin Reverse Opioid-Induced Respiratory Depression in Isoflurane Anesthetized Rats

Intravenous and Intratracheal Thyrotropin Releasing Hormone and Its Analog Taltirelin Reverse Opioid-Induced Respiratory Depression in Isoflurane Anesthetized Rats

BTBR Ob/Ob Mutant Mice Model Progressive Diabetic Nephropathy

A novel model mouse for type 2 diabetes mellitus with early onset and persistent hyperglycemia

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