Food intake rather than blood glucose levels affects the pharmacokinetic profile of insulin aspart in pigs

Author(s):  
Anna Katrina Jógvansdóttir Gradel ◽  
Jonas Kildegaard ◽  
Trine Porsgaard ◽  
Jens Lykkesfeldt ◽  
Hanne Hoffman Frølund Refsgaard
2021 ◽  
Vol 12 (1) ◽  
pp. 133-148
Author(s):  
Maryam Radahmadi ◽  
◽  
Mina Sadat Izadi ◽  
Atefeh Rayatpour ◽  
Maedeh Ghasemi ◽  
...  

Introduction: Corticotropin-Releasing Hormone (CRH) is involved in stress and energy homeostasis. On the other hand, CRH receptors also exist within the paraventricular nucleus (PVN) and Central Amygdala (CeA) nuclei. The present study compared the effect of CRH microinjections into PVN and CeA on three consecutive hours and cumulative food intake, internal regulatory factors of food intake, such as serum leptin and ghrelin, as well as blood glucose levels in rats under different acute psychological (Social Stress [SS] and Isolation Stress [IS] group) stresses. Methods: Sixty-six male Wistar rats were randomly allocated to 11 groups: Control, Sham, CRH-PVN, CRH-CeA, SS, IS, SS-CRH-PVN, SS-CRH-CeA, IS-CRH-PVN, and IS-CRH-CeA groups. The CRH (2 µg/kg in 0.5 µL saline) was injected into PVN and CeA nuclei in rats under everyday, acute social stress and isolation stress conditions. Results: Acute isolation and social stresses did not affect cumulative food intake. Whereas isolation stress led to changes in both leptin and glucose levels, social stress reduced only glucose levels. Cumulative food intake significantly decreased under acute CRH injection into the CeA and particularly into the PVN. Blood glucose significantly reduced in all the groups receiving CRH into their CeA. Conclusion: The PVN played a more important role compared to CeA on food intake. These nuclei probably employ different mechanisms for their effects on food intake. Besides, it seems that exogenously CRH injection into the PVN probably had a more anorectic effect than naturally activated CRH by stresses. Acute isolation stress had a greater impact than social stress on leptin level and cumulative food intake. Thus, elevated food intake related to leptin compared to ghrelin and glucose levels in the CRH-PVN group under acute social stress.


2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Katsunori Nonogaki ◽  
Miki Hazama ◽  
Noriko Satoh

Social isolation contributes to the development of obesity and insulin-independent diabetes in KKAymice. Here we show that systemic administration of liraglutide, a long-acting human glucagon-like peptide-1 (GLP-1) analog, significantly decreased food intake, body weight, and blood glucose levels at 24 h after its administration while having no significant effects on plasma insulin and glucagon levels in individually housed KKAymice. In addition, the systemic administration of liraglutide significantly increased plasma fibroblast growth factor (Fgf) 21 levels (1.8-fold increase) associated with increases in the expression of hepaticFgf21(1.9-fold increase) andPparγ(1.8-fold increase), while having no effects on the expression of hepaticPparαandFgf21in white adipose tissue. Moreover, systemic administration of liraglutide over 3 days significantly suppressed food intake, body weight gain, and hyperglycemia in KKAymice. On the other hand, despite remarkably increased plasma active GLP-1 levels (4.2-fold increase), the ingestion of alogliptin, a selective dipeptidyl peptidase-4 inhibitor, over 3 days had no effects on food intake, body weight, blood glucose levels, and plasma Fgf21 levels in KKAymice. These findings suggest that systemic administration of liraglutide induces hepatic Fgf21 production and suppresses the social isolation-induced obesity and diabetes independently of insulin, glucagon, and active GLP-1 in KKAymice.


Nutrients ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 3155
Author(s):  
Guojun Wu ◽  
Anna B. Liu ◽  
Yang Xu ◽  
Ying Wang ◽  
Liping Zhao ◽  
...  

Green tea extracts and tea catechins have been shown to prevent or alleviate diabetes. The present study tests the hypothesis that green tea leaves in powder form (GTP), which also contain fiber and other water non-extractable materials, are more effective than the corresponding green tea extracts (GTE) in impeding the development of diabetes in db/db mice. Female db/db mice were treated with a diet containing 1% of GTE, 2% of GTE, 2% of GTP (with the same catechin content as 1% GTE) or 1% GTP. The 1% GTE group had lower food intake, water consumption, body weight and fasting blood glucose levels than the control group, while 2% GTP did not have any significant effect. Dietary 1% GTE also preserved β-cell insulin secretion. However, 1% GTP increased food intake, water consumption and blood glucose levels. Microbiome analysis with 16S rRNA gene V4 sequencing showed that the gut microbiota was modified by GTE and GTP, and a few bacterial guilds were associated with blood glucose levels. In the Random Forest regression model, the leading predictor of metabolic outcome was food consumption, followed by changes in some bacterial guilds. The results illustrate the importance of food consumption and gut microbiota in affecting the progression of diabetes.


2016 ◽  
Vol 62 (1) ◽  
pp. 44-49 ◽  
Author(s):  
Ivan Nikolaevich Tiurenkov ◽  
Denis Vladimirovich Kurkin ◽  
Dmitry Aleksandrovich Bakulin ◽  
Elena Vladimirovna Volotova ◽  
Mikhail Ayratovich Chafeev

The search for new drugs for the treatment of type 2 diabetes mellitus (T2DM) and obesity remains an urgent problem. Drugs with influence on incretin system are widely used in the treatment of T2DM and obesity, since in addition to the hypoglycemic action of their inherent hypophagic effects. With the discovery of GPR119 receptor, there is the opportunity to pharmacological stimulation of endogenous secretion of incretins. Compound ZB-16 is active GPR119 agonist with IC50=7 nM. Its activation leads to increased secretion of the major incretins (GLP-1 and GIP), which are able to influence glucose metabolism and feeding behavior.Aims — to study the effect of GPR 119 receptor agonist compounds ZB-16 on blood glucose, body weight and food intake in rats with obesity.Material and methods.Male rats with initial weight 390—400 g were fed with high-carbohydrate and high-fat diet. During the next four weeks the animals orally received ZB-16 (1 mg/kg) and metformin (400 mg/kg) and then we assessed the level of water and food consumption, blood glucose levels, and performed oral glucose tolerance test (OGTT).Results.Compound ZB-16 and metformin reduced fasting blood glucose levels and weight of experimental animals, while the control rats gained weight. GPR119 agonist is more pronounced than metformin reduced the area under the curve «glucose of concentration—time» during the OGTT.Conclusions.Novel GPR119 agonist — ZB-16 is comparable to metformin in hypoglycemic and anorexigenic effect in animals with obesity caused high-carbohydrate and high-fat diet.


2007 ◽  
Vol 292 (5) ◽  
pp. R1775-R1781 ◽  
Author(s):  
Katsunori Nonogaki ◽  
Kana Nozue ◽  
Tomifusa Kuboki ◽  
Yoshitomo Oka

Milnacipran, a selective serotonin (5-HT) and norepinephrine (NE) reuptake inhibitor, increases extracellular 5-HT and NA levels equally in the central nervous system. Here, we report that systemic administration of milnacipran (20–60 mg/kg) significantly suppressed food intake after fasting in C57BL6J mice. The appetite-suppressing effects of milnacipran were sustained for 5 h. Neither SB242084, a selective 5-HT2C receptor antagonist, nor SB224289, a selective 5-HT1B receptor antagonist, reversed the appetite-suppressing effects of milnacipran. Milnacipran suppressed food intake and body weight in wild-type mice and in Ay mice, which have ectopic expression of the agouti protein. Moreover, milnacipran significantly increased hypothalamic proopiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) mRNA levels, while having no effect on hypothalamic neuropeptide Y, ghrelin, corticotropin-releasing hormone (CRH), and suppressor of cytokine signaling-3 mRNA levels. Interestingly, milnacipran did not increase plasma corticosterone and blood glucose levels, whereas fenfluramine, which inhibits 5-HT reuptake and stimulates 5-HT release, significantly increased plasma corticosterone and blood glucose levels in association with increased hypothalamic CRH mRNA levels. The appetite-suppressing effects of milnacipran had no effects on food intake in food-restricted, wild-type mice and Ay mice. On the other hand, fenfluramine suppressed food intake in food-restricted wild-type mice, but it had no effects in food-restricted Ay mice. These results suggest that inhibition of 5-HT and NA reuptake induces appetite-suppressing effects independent of 5-HT2C and 5-HT1B receptors, and increases hypothalamic POMC and CART gene expression without increasing plasma corticosterone and blood glucose levels in mice.


2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Grace Farhat ◽  
Lauren Moore ◽  
Inaki Moya ◽  
Lindsay Hall ◽  
Victoria Berset

AbstractNon-nutritive sweeteners (NNS) are suggested to reduce sugar and energy content of diet, but there is growing evidence that they can exacerbate obesity and diabetes through increasing appetite and energy intake. Stevia (stevioside extract), a natural sweetener, is being increasingly consumed, yet limited studies have looked at their effects on satiety and energy intake. The aim of this study is to investigate the effects of preloads of stevia on food intake, satiety and postprandial blood glucose levels when compared to water and sugar. Thirty participants (10 males/20 females; 26 ± 10.5 years; BMI: 23.44 ± 3.42 Kg/m2) took part in a three-arm single-blinded crossover trial. On separate test days, they received three different preloads (300 ml) containing water, sugar (60g) and stevia (1g) followed by an ad-libitum pizza lunch after 30 minutes. Breakfast was standardized. Blood glucose samples were collected before preload and lunch, and then at 30-minute intervals until 120 min post lunch. Volunteers recorded their feelings of satiety and hunger on visual analogue scales (VAS) before preload and after meal intake. A one-day diet diary was collected for each test day. Data was analysed using repeated measures ANOVA (SPSS Inc., Chicago, IL, USA). Despite the difference in energy content between preloads, there were no significant differences in energy intake at lunch between the three interventions (F (2, 56) = 0.25, p = 0.78). Furthermore, participants did not compensate by consuming more energy during the day after the stevia preload (1660 ± 584 Kcal) compared to sugar preload (1770 ± 763 Kcal, p = 0.82). There were no significant differences in VAS scores between stevia and sugar preloads, but participants scored significantly higher rates of hunger (before and after lunch) and desire to eat (before lunch) following water preload (p < 0.05). No significant differences between water, sugar and stevia were noted for postprandial glucose levels (120 min post lunch) when adjusted from baseline (F (2, 58) = 2.56, p = 0.09). Area under the curve (AUC) for glucose did not differ between water and stevia (p = 0.2). Results are in line with several clinical trials showing that the consumption of sweeteners does not lead to an increase in hunger and energy intake, and could therefore present a useful strategy to assist with weight loss. Further studies looking at long-term effects of stevia on weight regulation are needed to support these findings.


2010 ◽  
Vol 298 (2) ◽  
pp. E337-E345 ◽  
Author(s):  
Peilin Chen ◽  
Joan Vaughan ◽  
Cindy Donaldson ◽  
Wylie Vale ◽  
Chien Li

Urocortin 3 (Ucn 3) is a corticotropin-releasing factor (CRF)-related peptide with high affinity for the type 2 CRF receptor (CRFR2). Central administration of Ucn 3 stimulates the hypothalamic-pituitary-adrenal axis, suppresses feeding, and elevates blood glucose levels, suggesting that activation of brain CRFR2 promotes stress-like responses. Several CRFR2-expressing brain areas, including the ventromedial hypothalamus (VMH) and the posterior amygdala (PA), may be potential sites mediating the effects of Ucn 3. In the present study, Ucn 3 or vehicle was bilaterally injected into the VMH or PA, and food intake and plasma levels of ACTH, corticosterone, glucose, and insulin were determined. Food intake was greatly reduced in rats following Ucn 3 injection into the VMH. Ucn 3 injection into the VMH rapidly elevated plasma levels of glucose and insulin but did not affect ACTH and corticosterone secretion. Injection of Ucn 3 into the PA did not alter any of the parameters measured. We determined that the majority of CRFR2-positive neurons in the VMH were excitatory glutamatergic, and a subset of these neurons project to the arcuate nucleus of the hypothalamus (ARH). Importantly, stimulation of CRFR2 in the VMH increased proopiomelanocortin mRNA expression in the ARH. In conclusion, the present study demonstrates that CRFR2 in the VMH mediates some of the central effects of Ucn 3, and the ARH melanocortin system may be a downstream target of VMH CRFR2 neurons.


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