Inhibiting the Absorption of Dietary Carbohydrates and Fats with Natural Products
Christophe Wiart in Medicinal Plants in Asia for Metabolic Syndrome, 2017
Saponin fraction of roots of Platycodon grandiflorus (Jacq.) A. DC. (containing Platycodin D 25.1 mg/g) given as part of diet (0.5 g/100 g diet) for 6 weeks reduced food intake, prevented weight loss, decreased fasting plasma glucose by 37%, and improved glucose tolerance in diabetic rodents (db/db mice).143 This regimen reduced the activity of maltase and sucrase by 41%.143In vitro, the fraction inhibited yeast α-glucosidase activity by 79% at concentrations of 10 mg/mL. In addition, the fraction was a more effective α-glucosidase inhibitor than acarbose at the same concentration and this effect was superior to acarbose at 5 mg/mL.143 Db/db mice have a mutated leptin-receptor gene resulting in the increase of food intake and used as a model of obesity and diabetes. These mice are obese, hyperglycemic, hyperlipidemic, have increased plasma insulin and insulin resisitance.144Platycodon grandiflorus (Jacq.) A. DC. could be of value in the treatment of metabolic syndrome and clinical trials are warranted.
Energy balance and its regulation
Geoffrey P. Webb in Nutrition, 2019
In 1997, the first two cases of people with obesity caused by mutations in their leptin genes were identified; two British cousins of Pakistani origin. These are the apparent human equivalents of ob/ob mice. These two children were extremely obese, at 8 years the girl weighed 86 kg while the boy weighed 29 kg at 2 years old. There are technical reasons why one would expect that this mutation would be expected to be extremely rare in humans. It is thus no coincidence that these children were from a close-knit immigrant community with a history of consanguineous marriage which increases the chances of people being homozygous for any rare harmful recessive trait and thus having a genetic disease. According to Friedman and Halaas (1998), only about 5–10% of obese humans may have relatively low leptin levels. One group who are particularly prone to obesity, the Pima Indians, tend to have low leptin levels, which may explain their extreme propensity to obesity. The first identified cases of people who were obese because they had a mutation in their leptin receptor gene, the human equivalent of db/db mice, were three members of a French immigrant family.
Noninsulin-Dependent Animal Models of Diabetes Mellitus
John H. McNeill in Experimental Models of Diabetes, 2018
When expressed on the C57BL/KsJ background, db mice are obese, hyperphagic, exhibit low energy expenditure, and are severely hyperglycemic and diabetic.23,24 Plasma insulin is increased as early as 10 days, and peaks at six to ten times normal by 2 to 3 months, when animals are severely hyperglycemic. Insulin levels drop rapidly to near normal values, at which time islets are hyperplastic and hypertrophic. This is followed by progressive degranulation and necrosis, and the islet insulin content becomes greatly reduced. Glucose-induced insulin secretion is severely decreased, and there is a rapid rise in blood glucose to over 22 mM until death at 5 to 8 months of age.23,24 Hyperglycemia in the db/db mouse is more severe than in the ob/ob mouse, and animals show vascular abnormalities. Mice with a second allele, db2J, exhibit mild diabetes but greatly elevated insulin levels throughout life. The phenotypic expression is very similar to the C57BL/6J ob mouse. However, when the db2J allele is introduced onto the C57BL/KsJ background, offspring are indistinguishable from the db animals, emphasizing the importance of genetic background on gene expression.5 The db3J mutation, arose in the 129/J mouse strain and has severe obesity, hypoglycemia rather than hyperglycemia, marked hyperinsulinemia, and greatly enlarged islets.23,24
The olive constituent oleuropein exerts nephritic protective effects on diabetic nephropathy in db/db mice
Published in Archives of Physiology and Biochemistry, 2022
Six-week-old C57BL/KsJ WT nondiabetic (db/m) mice (18–20 g) and weight-matched genetically obese leptin receptor-deficient mice (db/db) which carried a point mutation in the leptin receptor and can develop obesity and type 2 diabetes spontaneously, were purchased from Model Animal Research Centre of Nanjing University. Animals were housed 5 per cage, provided with distilled water and food ad libitum, and kept under a 12 h light/dark cycle. When the blood glucose of db/db mice reached more than 11.0 mM, db/db mice were allocated into two groups: WT, db/db mice (1% carboxymethylcellulose sodium salt in saline), db/db mice + oleuropein (98%, C25H32O13) (Sigma-Aldrich, St. Louis, MO, USA). The WT db/m mice with normal diet were used as normal control. The two groups of db/db mice were fed with or without a daily oral gavage of 20 mg/kg of oleuropein for a total of 10 weeks. At the end of the experiment, blood samples and spot urines from each mouse were collected immediately before death. Kidney tissues were cut into two parts with one part snap frozen in liquid nitrogen and stored at −80 °C and the other part was fixed with 10% formalin in phosphate buffered saline (PBS). The fixed tissues were processed and embedded in paraffin. Relevant animal procedures were approved by the Animal Care and Use Committees of Anhui Province Hospital Affiliated to Anhui Medical University.
From leptin to lasers: the past and present of mouse models of obesity
Published in Expert Opinion on Drug Discovery, 2021
Joshua R. Barton, Adam E. Snook, Scott A. Waldman
Ten years later, Coleman’s first parabiosis experiments coupled a db/db mouse to a wild type C57Bl/KsJ mouse in search of a factor that might sensitize the db/db animals to insulin and normalize their blood sugar [22]. These conventional parabiosis studies measured the effect of shared circulation on the mice during parabiosis. Instead of rescuing the diabetic phenotype, parabiosis between db/db and wild type mice lead to the starvation and swift death (median survival time 23 days) of the wild type animals. Similar results had been found in a parabiosis study 10 years earlier, where rats with hypothalamic lesions had been surgically fused with uninjured rats [23]. Rats with bilateral ventromedial hypothalamic lesions overeat, gain weight, and become obese. Healthy, lesion-less rats coupled to obese, lesioned rats suffered the same fate as the wild type mice coupled to db/db mice: anorexia and eventual death. These studies led to the hypothesis that db/db and lesioned mice overproduced a satiety factor to which they were somehow unable to respond. The hypothalamic lesioning experiments implied that receptors for the satiety response were located in the ventromedial hypothalamus.
PPAR-δ Activation Ameliorates Diabetes-Induced Cognitive Dysfunction by Modulating Integrin-linked Kinase and AMPA Receptor Function
Published in Journal of the American College of Nutrition, 2019
Engy A. Abdel-Rahman, Subhrajit Bhattacharya, Manal Buabeid, Mohammed Majrashi, Jenna Bloemer, Ya-Xiong Tao, Muralikrishnan Dhanasekaran, Martha Escobar, Rajesh Amin, Vishnu Suppiramaniam
Due to the body condition of db/db mice (i.e., increased body weight and reduced mobility), the possibility that the extent to which exploratory behavior may be compromised due to decreased general activity or increased anxiety in a novel environment was determined by analyzing the number of alternations animals made within the maze. Number of alternations analyzed with one-way ANOVA showed that vehicle-treated wild-type mice produced more alternations than vehicle-treated db/db mice (F(2,10) = 26.79, MSE = 29.87, p < 0.001, Figure 1C; all F(1,10) = 48.21, n = 5, p < 0.001). However, the vehicle-treated and GW0742-treated db/db mice did not differ in this measure (F(1,10) < 0.10). Thus, although non-diabetic wild-type mice showed more activity and general exploratory behavior than vehicle-treated and GW0742-treated db/db mice, mobility was not a concern when comparing the two db/db mouse groups.
Related Knowledge Centers
- Cluster of Differentiation
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- Receptor
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