scholarly journals Sex-Specific ADHD-Like Behaviour, Altered Metabolic Functions, and Altered EEG Activity in Sialyltransferase ST3GAL5-Deficient Mice

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1759
Author(s):  
Tatyana Strekalova ◽  
Ekaterina Veniaminova ◽  
Evgeniy Svirin ◽  
Ekaterina Kopeikina ◽  
Tatyana Veremeyko ◽  
...  

A deficiency in GM3-derived gangliosides, resulting from a lack of lactosylceramide-alpha-2,3-sialyltransferase (ST3GAL5), leads to severe neuropathology, including epilepsy and metabolic abnormalities. Disruption of ganglioside production by this enzyme may also have a role in the development of neuropsychiatric disorders. ST3Gal5 knock-out (St3gal5−/−) mice lack a-, b-, and c-series gangliosides, but exhibit no overt neuropathology, possibly owing to the production of compensatory 0-series glycosphingolipids. Here, we sought to investigate the possibility that St3gal5−/− mice might exhibit attention-deficit/hyperactivity disorder (ADHD)-like behaviours. In addition, we evaluated potential metabolic and electroencephalogram (EEG) abnormalities. St3gal5−/− mice were subjected to behavioural testing, glucose tolerance tests, and the levels of expression of brain and peripheral A and B isoforms of the insulin receptor (IR) were measured. We found that St3gal5−/− mice exhibit locomotor hyperactivity, impulsivity, neophobia, and anxiety-like behavior. The genotype also altered blood glucose levels and glucose tolerance. A sex bias was consistently found in relation to body mass and peripheral IR expression. Analysis of the EEG revealed an increase in amplitude in St3gal5−/− mice. Together, St3gal5−/− mice exhibit ADHD-like behaviours, altered metabolic and EEG measures providing a useful platform for better understanding of the contribution of brain gangliosides to ADHD and associated comorbidities.

1969 ◽  
Vol 62 (3) ◽  
pp. 438-448 ◽  
Author(s):  
R. L. Fenichel ◽  
R. M. Purse ◽  
H. E. Alburn ◽  
R. A. Edgren

ABSTRACT Treatment of adult female spayed rats with norgestrel, ethynyl oestradiol and their combination (Ovral®) at doses approximating 1 and 25 fold multiples of the human dose protected them against the combined diabetogenic influence of a glucose load and the hyperglycaemic effect of reduced insulin B-chain. Norgestrel and Ovral® appeared to be antidiabetogenic since they reversed the B-chain-induced hyperglycaemia. Various steroidal contraceptives and certain of their components failed to modify B-chain-induced hyperglycaemia in spayed rats sensitized with a high fat, high protein diet. Normal intact female rats treated with norgestrel, ethynyl oestradiol and their combinations and given glucose tolerance tests produced glucose responses higher than those of controls, but since these groups showed recovery to or toward control blood glucose levels, insulin mobilization was apparently normal. In a second experiment, Ovral® and various contraceptive formulations failed to produce significant alterations in glucose tolerance. None of these studies suggested a diabetogenic effect of the contraceptive steroids employed; in fact, the first study with reduced insulin B-chain suggested an anti-diabetogenic effect for Ovral®.


1973 ◽  
Vol 72 (3) ◽  
pp. 475-494 ◽  
Author(s):  
Svein Oseid

ABSTRACT Six cases of congenital generalized lipodystrophy have been studied at different ages from infancy to adolescence with regard to glucose tolerance, insulin secretion, and insulin sensitivity. During the first few years of life there is normal glucose tolerance. The fasting immuno-reactive insulin (IRI) levels are either slightly elevated or normal. The IRI response to glucose is exaggerated and prolonged, at least from the third year of life. Some degree of insulin resistance is already present in infancy. From the age of 8–10 years glucose tolerance decreases rapidly. The fasting IRI levels are usually grossly elevated, while fasting plasma glucose levels are only moderately elevated or normal. The IRI responses to oral and iv administered glucose, and to tolbutamide are exaggerated; the insulinogenic indices are high. Cortisone primed glucose tolerance tests become abnormal. Insulin resistance is marked, and increases with age. After cessation of growth at approximately 12 years of age, frank diabetes with fasting hyperglycaemia and diabetic glucose tolerance curves developed in the one patient followed beyond this age. Her fasting IRI was increased, but there was a poor IRI response to glucose stimulation, suggesting a partial exhaustion of the β-cells. Her initial IRI response to tolbutamide was still good, but not as brisk as in the younger patients. This type of diabetes is quite different from the juvenile form, and also from the diabetes of older age. It may be causally related to the lack of an adequate adipose organ necessary for the disposal of excesses of glucose, or possibly related to another anti-insulin mechanism.


2019 ◽  
Vol 19 (3) ◽  
pp. 292-301
Author(s):  
Omar Farid ◽  
Naoufel Ali Zeggwagh ◽  
Fadwa EL Ouadi ◽  
Mohamed Eddouks

Objective: The aim of this work was to evaluate the antihyperglycemic activity of aerial parts aqueous extract (A.P.A.E) of Mentha pulegium (M. pulegium) on blood glucose levels in normal and streptozotocin(STZ)-induced diabetic rat. The glucose tolerance was evaluated in normal rats. Moreover, the histological sections and morphometric analysis at the liver and pancreas have been carried out in this investigation both in normal and STZ-diabetic rats. Methods: The effect of A.P.A.E of M. pulegium (20 mg/kg) on blood glucose levels was investigated in normal and diabetic rats (n=6). Histopathological changes in liver and pancreas were examined under phase contrast microscope and a preliminary screening for various bioactive constituents was realized according to standard methods. Key Findings: Both single and repeated oral administration of A.P.A.E (20 mg/kg) caused a significant reduction in blood glucose levels in STZ-diabetic rats (p<0.0001). The morphometric analysis and histological sections realized in pancreas and liver have showed the beneficial effect of the A.P.A.E in cellular population. According to oral glucose tolerance test (OGTT), the aqueous extract has revealed an improvement of glucose tolerance in normal rat. Furthermore, the preliminary phytochemical screening of A.P.A.E of M. pulegium has demonstrated the presence of various metabolite compounds including polyphenols, flavonoids, terpenoids tannins, cyanidins, sesquiterpenes, and glycosides. Conclusion: We conclude that the A.P.A.E of M. pulegium (20 mg/kg) exhibits a potent antihyperglycemic activity in STZ diabetic rats.


2015 ◽  
Vol 10 (2) ◽  
pp. 326 ◽  
Author(s):  
Emordi Jonathan Emeka ◽  
Agbaje Esther Oluwatoyin ◽  
Oreagba Ibrahim Adekunle ◽  
Iribhogbe Osede Ignis

<p>The purpose of this study is to evaluate the hypoglycaemic properties and preliminary phytochemical screening of <em>Uveria chamae</em>. The hypoglycaemic properties of <em>Uveria chamae</em> was assessed on normoglycaemic rat that received single dose of the extract at 250 and 500 mg/kg body weight and blood glucose levels estimated at 2, 4, and 6 hours (single dose study). The hypoglycaemic property of the extract was also evaluated in normoglycemic rats by oral glucose tolerance test. Phytochemical screening of the extract for the presence of secondary metabolites was performed with standard methods. The extract showed a significant (p&lt;0.05) reduction in blood glucose levels at 2h and 6h compared to control.  The oral glucose tolerance test  result also showed a significant decrease (p&lt;0.05) in blood glucose levels . The study showed that the extract, <em>Uveria chamae</em> has hypoglycaemic properties which may be accounted for by the presence of the phytochemicals.</p><p> </p>


2003 ◽  
Vol 80 (4) ◽  
pp. 1022-1025
Author(s):  
Michael P Diamond ◽  
Subodhsingh Chauhan ◽  
Michael Kruger ◽  
Marappa Subramanian

2004 ◽  
Vol 279 (44) ◽  
pp. 45803-45809 ◽  
Author(s):  
Yoshihisa Nakatani ◽  
Hideaki Kaneto ◽  
Dan Kawamori ◽  
Masahiro Hatazaki ◽  
Takeshi Miyatsuka ◽  
...  

The c-Jun N-terminal kinase (JNK) pathway is known to be activated under diabetic conditions and to possibly be involved in the progression of insulin resistance. In this study, we examined the effects of modulation of the JNK pathway in liver on insulin resistance and glucose tolerance. Overexpression of dominant-negative type JNK in the liver of obese diabetic mice dramatically improved insulin resistance and markedly decreased blood glucose levels. Conversely, expression of wild type JNK in the liver of normal mice decreased insulin sensitivity. The phosphorylation state of crucial molecules for insulin signaling was altered upon modification of the JNK pathway. Furthermore, suppression of the JNK pathway resulted in a dramatic decrease in the expression levels of the key gluconeogenic enzymes, and endogenous hepatic glucose production was also greatly reduced. Similar effects were observed in high fat, high sucrose diet-induced diabetic mice. Taken together, these findings suggest that suppression of the JNK pathway in liver exerts greatly beneficial effects on insulin resistance status and glucose tolerance in both genetic and dietary models of diabetes.


2019 ◽  
pp. 146-155
Author(s):  
AA Salako ◽  
OA Adenowo ◽  
OE Amoran ◽  
O Odusan ◽  
GJ Mautin ◽  
...  

Background: Emerging patterns in epidemiological transitions have led to increased risk for Non-Communicable Diseases and infectious conditions globally. Diabetes mellitus (DM) in a population is one such risk factor that could lead to the development of Tuberculosis (TB) due to weakened immune functions in affected persons, with implications for mortality. If not diagnosed early, DM also leads to poor treatment outcomes in TB. Objective: To assess the prevalence of DM and impaired glucose tolerance (pre-diabetes) among newly diagnosed tuberculosis cases in Ijebu-Ode Local Government Area of Ogun State, Nigeria. Methods: This cross-sectional study was conducted among 100 newly diagnosed Pulmonary TB patients in ljebu-Ode LGA. The patients were selected from four health facilities and were screened for elevated Fasting Blood Glucose levels using a laboratory spectrophotometer (glucose oxidase method). Results: The mean age of the 100 study participants was 33 years (± 9.82), with ages within 19 -62 years. Eleven (11.0%) had elevated blood glucose levels suggestive of DM, while 20 (20.0%) had impaired fasting blood glucose levels. Among these 31 patients, 18 (58.0%) were males while 13 (42.0%) were females. The modal ages were within 20-39 years. Conclusion: Screening for DM by healthcare providers should be routinely conducted before commencing TB patients on treatment. This will aid early detection, improve treatment outcomes of TB and prevent mortality among patients with these co-morbidities.


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