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Spontaneously Diabetic Torii (SDT) Fatty Rat, a Novel Animal Model of Type 2 Diabetes Mellitus, Shows Blunted Circadian Rhythms and Melatonin Secretion.

ABSTRACT: In patients with diabetes mellitus (DM), impairments of circadian rhythms, including the sleep-wake cycle, blood pressure, and plasma melatonin concentrations, are frequently observed. Animal models of DM are also reported to show aberrant circadian rhythms. However, the changes in the circadian rhythms of plasma soluble substances, including melatonin, in diabetic animals are controversial. In the present study, we investigated the circadian rhythms of spontaneous locomotor activity, metabolic parameters (plasma glucose, triglyceride, and total cholesterol), and plasma melatonin concentrations in Spontaneously Diabetic Torii (SDT) fatty rats, a novel animal model of type 2 DM. Although SDT fatty rats exhibited low locomotor activity in the dark phase, no phase shifts were observed. The circadian variations of plasma metabolic parameters were more apparent in the SDT fatty rats compared with control Sprague-Dawley (SD) rats. The circadian rhythms of plasma melatonin concentrations were significantly impaired in SDT fatty rats. To get an insight into the mechanism underlying the impaired melatonin secretion in SDT fatty rats, the expression of arylalkylamine N-acetyltransferase (Aanat) and acetylserotonin O-methyltransferase (Asmt) mRNA, which encode the rate-limiting enzymes for melatonin synthesis, was investigated in the pineal gland. There were no significant differences in Aanat and Asmt expression between the control SD and SDT fatty rats. These results suggest that SDT fatty rats show impaired circadian rhythms and dysregulated melatonin secretion.

SUBMITTER: Sakimura K

PROVIDER: S-EPMC6174757 | biostudies-other | 2018

REPOSITORIES: biostudies-other

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Spontaneously Diabetic Torii (SDT) Fatty Rat, a Novel Animal Model of Type 2 Diabetes Mellitus, Shows Blunted Circadian Rhythms and Melatonin Secretion.

Sakimura Katsuya K Maekawa Tatsuya T Kume Shin-Ichi SI Ohta Takeshi T

International journal of endocrinology 20180923

In patients with diabetes mellitus (DM), impairments of circadian rhythms, including the sleep-wake cycle, blood pressure, and plasma melatonin concentrations, are frequently observed. Animal models of DM are also reported to show aberrant circadian rhythms. However, the changes in the circadian rhythms of plasma soluble substances, including melatonin, in diabetic animals are controversial. In the present study, we investigated the circadian rhythms of spontaneous locomotor activity, metabolic ...[more]

PMID: 30344606

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Project description:ObjectivesThe circadian system modulates many important physiologic processes, synchronizing tissue-specific functions throughout the body. We sought to characterize acute alterations of circadian rhythms in critically ill patients and to evaluate associations between brain dysfunction, systemic multiple organ dysfunction, environmental stimuli that entrain the circadian rhythm (zeitgebers), rest-activity rhythms, and the central circadian rhythm-controlled melatonin secretion profile.DesignProspective study observing a cohort for 24-48 hours beginning within the first day of ICU admission.SettingMultiple specialized ICUs within an academic medical center.PatientsPatients presenting from the community with acute onset of either intracerebral hemorrhage as a representative neurologic critical illness or sepsis as a representative systemic critical illness. Healthy control patients were studied in using modified constant routine in a clinical research unit.InterventionsNone.Measurements and main resultsLight, feeding, activity, medications, and other treatment exposures were evaluated along with validated measures of encephalopathy (Glasgow Coma Scale), multiple organ system function (Sequential Organ Failure Assessment score), and circadian rhythms (profiles of serum melatonin and its urinary metabolite 6-sulphatoxymelatonin). We studied 112 critically ill patients, including 53 with sepsis and 59 with intracerebral hemorrhage. Environmental exposures were abnormal, including light (dim), nutritional intake (reduced or absent and mistimed), and arousal stimuli (increased and mistimed). Melatonin amplitude and acrophase timing were generally preserved in awake patients but dampened and delayed with increasing encephalopathy severity. Melatonin hypersecretion was observed in patients exposed to catecholamine vasopressor infusions, but unaffected by sedatives. Change in vasopressor exposure was the only factor associated with changes in melatonin rhythms between days 1 and 2.ConclusionsEncephalopathy severity and adrenergic agonist medication exposure were the primary factors contributing to abnormal melatonin rhythms. Improvements in encephalopathy and medical stabilization did not rapidly normalize rhythms. Urinary 6-sulphatoxymelatonin is not a reliable measure of the central circadian rhythm in critically ill patients.

Dataset Information

Spontaneously Diabetic Torii (SDT) Fatty Rat, a Novel Animal Model of Type 2 Diabetes Mellitus, Shows Blunted Circadian Rhythms and Melatonin Secretion.

Publications

Spontaneously Diabetic Torii (SDT) Fatty Rat, a Novel Animal Model of Type 2 Diabetes Mellitus, Shows Blunted Circadian Rhythms and Melatonin Secretion.

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