Gastric Emptying in Animal Models of Human Diabetes: Correlation to Blood Glucose Level and Gut Neuroendocrine Peptide Content

Spångéus, Anna

doi:10.3109/2000-1967-132

Cited by 22 publications

(18 citation statements)

References 20 publications

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“…This model of diabetes has been reported clinically [34]. The ob/ob mice used in this study are 12 weeks old, consistent with use in other studies: male ob/ob mice (6-15 weeks old) and male mice fed high fat diet (from 14-33 weeks) exhibit gastroparesis with continued elevated plasma glucose [35][36][37], and 15 week old male ob/ob mice exhibit slowed gastrointestinal transit [2,38].…”

Section: Discussionsupporting

confidence: 85%

Dietary Genistein Rescues Reduced Basal Chloride Secretion in Diabetic Jejunum via Sex-Dependent Mechanisms

Catmull¹,

Masood²,

Schacht³

et al. 2016

Cell Physiol Biochem

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Background/Aims: The goal of this study was to determine the effect of dietary genistein (naturally occurring phytoestrogen) on jejunal secretory function in a clinically relevant model of diabetes and obesity, the leptin-defIcient ob/ob mouse. Methods: We measured transepithelial short circuit current (I_sc), across freshly isolated segments of jejunum from 12-week old male and female ob/ob and lean C57Bl/6J mice fed a genistein diet (600 mg genistein/kg diet) for 4-weeks. Separate segments of jejunum were frozen for western blot determination of key proteins involved in secretory transport. Results: Basal I_sc was signifIcantly decreased (by 33%, P<0.05) in ob/ob females versus leans, and genistein-diet reversed this. Similarly, in males, basal I_sc was decreased (by 47%, P<0.05) in ob/ob mice versus leans, and genistein-diet reversed this. Inhibition with either clotrimazole (100 µM, bilateral) or ouabain (100 µM, basolateral) was signifIcantly reduced in ob/ob mice compared to leans (P<0.05), and genistein-diet reversed clotrimazole-sensitive inhibition in ob/ob females, and reversed the ouabain-sensitive inhibition in males (indicating sex-dependent mechanisms). Our data suggested that PDE3 levels were dysregulated in ob/ob females and genistein reversed this. Expression of total CFTR (normalized to actin) was signifIcantly decreased ∼80% (P<0.05) in all ob/ob mice compared to leans, and genistein-diet was without effect. Expression of total NKCC1 (normalized to actin) was signifIcantly decreased ∼80% (P<0.05) in ob/ob male mice versus leans, and genistein-diet reversed this. Conclusions: Our data suggests that the reduced basal jejunal I_sc in ob/ob female mice is a consequence of reduced CFTR expression, decreased activities of the basolateral K_Ca channel and Na⁺/K⁺-ATPase, and in male mice reduced basal jejunal I_sc is a consequence of reduced CFTR and NKCC1 expression, along with decreased activities of the basolateral K_Ca channel and Na⁺/K⁺-ATPase. Genistein-diet has beneficial effects on basal I_sc mediated by sex-dependent mechanisms in diabetic mice: in females via increased K_Ca-sensitive I_sc and in males via increased Na⁺/K⁺-ATPase activity and increased NKCC1 expression. Improved understanding of intestinal dysfunctions in the ob/ob jejunum, may allow for the development of novel drug targets to treat obesity and diabetes, and may also be of benefit in CF-related diabetes.

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Section: Discussionsupporting

confidence: 85%

Dietary Genistein Rescues Reduced Basal Chloride Secretion in Diabetic Jejunum via Sex-Dependent Mechanisms

Catmull¹,

Masood²,

Schacht³

et al. 2016

Cell Physiol Biochem

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“…Somatostatin is one of the most important regulators of the HPT axis, due to its suppression of TRH and TSH secretion [44,45]. There is evidence that in DM1 somatostatin level can be increased, as shown in human DM1 and in the gastrointestinal tract of nonobese diabetic mice [46][47][48], or can be unchanged or reduced, as demonstrated in rats with STZ-induced DM [49][50][51].…”

Section: Endocrine Researchmentioning

confidence: 99%

The Influence of Intranasal Insulin on Hypothalamic-Pituitary-Thyroid Axis in Normal and Diabetic Rats

et al. 2015

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The functions of hypothalamic-pituitary-thyroid axis are attenuated in type 1 diabetes mellitus due to insulin deficiency. The use of intranasally administered insulin is of considerable interest for treatment of diabetes and cognitive disorders, but its effect on the thyroid system has not been investigated yet. We studied the influence of long-term treatment with intranasal insulin on the hypothalamic-pituitary-thyroid axis of nondiabetic rats and diabetic animals with streptozotocin models of acute and mild type 1 diabetes mellitus. This treatment was carried out for 28 days in acute (daily does of 0.3, 0.6, and 1.5?IU of insulin per rat) and for 135 days in mild diabetes (daily dose of 0.45?IU/rat). Nondiabetic rats were treated in a similar manner. Intranasal insulin in both models of diabetes resulted in the improvement of thyroid status; manifested as increase of thyroid hormones levels and restoration of response to thyroliberin. In acute diabetes, a daily dose of 0.6?IU/rat was the most effective. Twenty eight days treatment of nondiabetic rats with intranasal insulin at a dose of 0.3?IU/rat resulted in a significant increase of free and total thyroxine levels. Longer treatment of rats with mild diabetes and nondiabetic animals significantly increased thyrotropin level. Thus, long-term intranasal insulin treatment restored the hypothalamic-pituitary-thyroid axis function in type 1 diabetes, but led to a significant increase in the thyrotropin level, which must be considered when designing a strategy for the use of intranasal insulin in clinical applications.

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“…Others found increased pepsinogen I levels consequently elevating pepsin in gastric fluid [101]. In diabetic mice models the influence of somatostatin, peptide YY, substance P, vasoactive intestinal polypeptide (VIP) and galanin have been investigated [102]. Antral motility was lower during hyperglycaemia in non-obese diabetic mice, which was explained by decreased levels of motilin and pancreatic polypeptide [102].…”

Section: Neurohumoral Regulationmentioning

confidence: 99%

“…In diabetic mice models the influence of somatostatin, peptide YY, substance P, vasoactive intestinal polypeptide (VIP) and galanin have been investigated [102]. Antral motility was lower during hyperglycaemia in non-obese diabetic mice, which was explained by decreased levels of motilin and pancreatic polypeptide [102]. Besides these hormones, a variety of receptors have been identified on vagal afferents, which can either enhance (e.g.…”

Section: Neurohumoral Regulationmentioning

confidence: 99%

Gastroesophageal reflux disease in diabetic patients: a systematic review

et al. 2007

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Gastroösophageale Refluxkrankheit bei Diabetikern: eine systematische Ü bersichtZusammenfassung. Grundlagen: Diabetes mellitus (DM) und die Gastroö sophageale Refluxkrankheit (GERD) sind in der westlichen Welt durch eine rasch steigende Inzidenz charakterisiert, die enorme Kosten verursachen. DM betrifft etwa 10% der Bevö lkerung, wä hrend GERDSymptome und Refluxö sophagitis bei rund 40% bzw. 20% beschrieben wurden.Methodik: Dieser Ü bersichtsartikel fasst den derzeitigen Wissensstand ü ber GERD bei Diabetikern zusammen und legt ein besonderes Augenmerk auf Symptome, diagnostische Ergebnisse, pathophysiologische Zusammenhä nge und Therapieoptionen. Der Evidenzgrad ist gering, da es sich bei den meisten Arbeiten um Fall-Kontrollstudien mit limitierter Patientenzahl (Evidenz-Level IIIb) und Fallserien (Evidenz-Level IV) handelt.Ergebnisse: Refluxsymptome werden bei rund 50% der Diabetiker beschrieben, wobei sie bei Patienten mit oraler antidiabetischer Therapie am stä rksten ausgeprä gt sind. Lang bestehende Krankheitsdauer, schlechte Blutzuckereinstellung mit erhö hten HbA 1c -Werten und Ü bergewicht verstä rken diese Beschwerden. Die erosive Ö sophagitis betrifft mehr als 40% der Diabetiker mit einer hö heren Prä valenz bei Vorliegen einer autonomen Neuropathie. PH-metrische Untersuchungen waren bei bis zu 90% symptomatischer Refluxpatienten pathologisch, wä hrend bislang widersprü chliche manometrische Ergebnisse beschrieben wurden. Vermehrte Magensä ure-, verminderte Bikarbonatund Speichelsekretion, gesteigertes Auftreten von transienten Sphinkterrelaxationen und ein verminderter Tonus des unteren Ö sophagussphinkters sind an der Entstehung der Refluxkrankheit ebenso beteiligt wie verminderte Ö sophagus-und Magenmotilitä t. Ü berdies ist die Heilung von Schleimhautverletzungen bei Diabetikern verzö gert. Daten zur Therapie der GERD bei Diabetikern mittels Protonenpumpenihibitoren sind ebenso wenig verfü gbar wie Studien ü ber die interventionelle oder chirurgische Behandlung dieser Patienten.Schlussfolgerungen: Es gibt einige Hinweise dafü r, dass Diabetes, unabhä ngig von Adipositas, ein Risikofaktor fü r die Entstehung der GERD ist. Spezifische pathophysiologische Mechanismen sind fü r die Genese der GERD bei Diabetikern von Bedeutung, was die Notwendigkeit weiterer Studien unterstreicht.Schlü sselwö rter: Gastroö sophageale Refluxkrankheit (GERD), Diabetes mellitus, Hyperglykä mie, Neuropathie, Ü bergewicht.Summary. Background: Diabetes mellitus (DM) and gastroesophageal reflux disease (GERD) are characterized by a rapidly increasing incidence within the Western World causing incredible costs. DM affects about 10% of the population, whereas GERD symptoms and GERD related esophagitis have been reported in 40% and 20%, respectively.Methods: This systematic review deals with the current knowledge on GERD in diabetic patients with special reference to symptoms, diagnostic outcomes, pathophysiologic characteristics and treatment strategies. The evidence level is low, as most of the contributions are individual ca...

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Gastric Emptying in Animal Models of Human Diabetes: Correlation to Blood Glucose Level and Gut Neuroendocrine Peptide Content

Cited by 22 publications

References 20 publications

Dietary Genistein Rescues Reduced Basal Chloride Secretion in Diabetic Jejunum via Sex-Dependent Mechanisms

Dietary Genistein Rescues Reduced Basal Chloride Secretion in Diabetic Jejunum via Sex-Dependent Mechanisms

The Influence of Intranasal Insulin on Hypothalamic-Pituitary-Thyroid Axis in Normal and Diabetic Rats

Gastroesophageal reflux disease in diabetic patients: a systematic review

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