98 THE FETAL AND POSTNATAL EFFECTS OF PERICONCEPTIONAL HYPERGLYCEMIA USING A RABBIT MODEL

2011 ◽  
Vol 23 (1) ◽  
pp. 154
Author(s):  
R. Brat ◽  
A. Rolland ◽  
R. Thieme ◽  
M. Dahirel ◽  
G. Boyer ◽  
...  

The objective of this study was to analyse the effects of maternal hyperglycemia during the periconception period on fetal and postnatal development using a rabbit model. Diabetes was induced in adult New Zealand female does by a single intravenous alloxan injection (group D). Glycemia was maintained between 3 and 5 g L–1 with 2 daily subcutaneous insulin injections. Does from group D and contemporary controls (group C) were naturally mated 1 wk after induction of diabetes in group D animals, without superovulation, and embryos collected after sacrifice on Day 4 post-coitum. In Expt. 1, embryos from D (n = 11) and C (n = 13) groups were transferred respectively to the right and left horns of 3 female recipients, which were killed on Day 28. In Expt. 2, 17 D and 16 C females were mated naturally. 68 D and 98 C embryos were collected and transferred to 26 non-diabetic recipients (6–7 embryos per doe). 17 females were pregnant with no difference between C and D recipients. Fetal development was monitored by ultrasound. At birth, litters were equilibrated in number. 15 D and 7 C pups (from 4 D and 2 C litters) were killed at weaning (1 month of age). The remaining 13 D and 26 C pups (4 D and 7 C litters) were allocated to 1 of 2 feeding groups: control or obesogenic diet. The obesogenic diet was based on the control diet supplemented with animal fat (suet, 200%) and glucose (200%). Bodyweight, adiposity, and glucose metabolism were monitored until sacrifice at 5 months of age. Data were analysed by ANOVA using litter (fetuses), litter and sex (weaning), and litter and diet (5 months) as co-factors. Sex effects at 5 months were not analysed due to small numbers of animals. Fetal development was not different between D and C groups. Fetal, placental, and fetal organ weights did not differ at Day 28, except for brain weight, which was significantly lower in D fetuses (0.86 ± 0.1 v. 1.05 ± 0.08 g; P < 0.05). There was no difference in litter size at birth (3.3 ± 0.3 v. 3.6 ± 0.5 pups for D and C groups, respectively; P = 0.5), but birthweight was significantly increased in D offspring (211 ± 6 v. 194 ± 6 g; P < 0.05). There was no difference in weight after 14 days. At 1 month of age, adiposity, plasma insulin and leptin concentrations were not different between groups. In contrast, in male D offspring, fasting glycemia was significantly lower (1.7 ± 0.2 v. 2.1 ± 0.02 g L–1; P < 0.01), plasma insulin-like growth factor 1 was significantly increased (P < 0.05) and kidney/bodyweight ratio was significantly reduced (0.41 ± 0.03 v. 0.45 ± 0.04; P < 0.01). From 12 wk of age, bodyweight became significantly different between D and C groups and according to diet (P < 0.005), with D individuals being lighter than C individuals for each dietary group. Finally, fasting glycemia was significantly higher in the animals fed the obesogenic diet (1.35 ± 0.05 v. 1.19 ± 0.05 g L–1; P < 0.04), regardless of group. These data suggest that maternal hyperglycemia during the periconceptional period affects glucose metabolism and organ development in offspring with sexual dimorphism.

2011 ◽  
Vol 47 (3) ◽  
pp. 261-271 ◽  
Author(s):  
Inagadapa J N Padmavathi ◽  
Kalashikam Rajender Rao ◽  
Manchala Raghunath

Robust evidence suggests that nutritional insult during fetal development could program the offspring to glucose intolerance, impaired insulin response and insulin resistance (IR). Considering the importance of chromium (Cr) in maintaining carbohydrate metabolism, this study determined the effect of maternal Cr restriction (CrR) on glucose metabolism and plasma insulin in Wistar/NIN (WNIN) rat offspring and the associated biochemical and/or molecular mechanisms. Female, weanling WNIN rats receivedad libitumfor 12 weeks, a control diet or the same with 65% restriction of Cr and mated with control males. Some of the Cr-restricted dams were rehabilitated from conception or parturition and their pups weaned on to control diet. At the time of weaning, half of the Cr restricted offspring were rehabilitated to control diet while others continued on Cr-restricted diet. Maternal CrR increased fasting plasma glucose, fasting insulin, homeostasis model assessment of IR, and area under the curve of glucose and insulin during oral glucose tolerance test in the offspring. Expression and activity of rate-limiting enzymes of glucose metabolism were comparable among different groups and expression of genes involved in insulin secretion was increased albeit in male offspring whereas antioxidant enzyme activities were decreased in offspring of both genders. Rehabilitation, in general, corrected the changes albeit partially. Maternal dietary CrR induced IR, impaired glucose tolerance in WNIN rat offspring and was associated with increased oxidative stress, which may predispose them to type 2 diabetes in their later life.


2018 ◽  
Vol 239 (3) ◽  
pp. 313-324 ◽  
Author(s):  
Lewin Small ◽  
Henry Gong ◽  
Christian Yassmin ◽  
Gregory J Cooney ◽  
Amanda E Brandon

One major factor affecting physiology often overlooked when comparing data from animal models and humans is the effect of ambient temperature. The majority of rodent housing is maintained at ~22°C, the thermoneutral temperature for lightly clothed humans. However, mice have a much higher thermoneutral temperature of ~30°C, consequently data collected at 22°C in mice could be influenced by animals being exposed to a chronic cold stress. The aim of this study was to investigate the effect of housing temperature on glucose homeostasis and energy metabolism of mice fed normal chow or a high-fat, obesogenic diet (HFD). Male C57BL/6J(Arc) mice were housed at standard temperature (22°C) or at thermoneutrality (29°C) and fed either chow or a 60% HFD for 13 weeks. The HFD increased fat mass and produced glucose intolerance as expected but this was not exacerbated in mice housed at thermoneutrality. Changing the ambient temperature, however, did alter energy expenditure, food intake, lipid content and glucose metabolism in skeletal muscle, liver and brown adipose tissue. Collectively, these findings demonstrate that mice regulate energy balance at different housing temperatures to maintain whole-body glucose tolerance and adiposity irrespective of the diet. Despite this, metabolic differences in individual tissues were apparent. In conclusion, dietary intervention in mice has a greater impact on adiposity and glucose metabolism than housing temperature although temperature is still a significant factor in regulating metabolic parameters in individual tissues.


Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 757
Author(s):  
Jennifer M. Monk ◽  
Wenqing Wu ◽  
Dion Lepp ◽  
K. Peter Pauls ◽  
Lindsay E. Robinson ◽  
...  

Cooked common beans (Phaseolus vulgaris) improve intestinal health in lean mice and attenuate intestinal dysbiosis and inflammation when consumed concurrent with obesity development. We determined the effects of a high-fat (HF) bean supplemented diet in mice with established obesity (induced by 12 weeks of HF diet (60% fat as kcal)) compared to obese mice consuming a HF or low-fat (LF) weight loss control diet. Obese C57BL/6 male mice remained consuming HF for eight weeks or were randomly switched from HF to an isocaloric HF with 15.7% cooked navy bean powder diet (HFàHFB) or LF (11% fat as kcal; HFàLF) (n = 12/group). HFàHFB improved the obese phenotype, including (i) fecal microbiome (increased Prevotella, Akkermansia muciniphila, and short-chain fatty acid levels), (ii) intestinal health (increased ZO-1, claudin-2, Muc2, Relmβ, and Reg3γ expression), and (iii) reduced adipose tissue (AT) inflammatory proteins (NFκBp65, STAT3, IL-6, MCP-1, and MIP-1α), versus HF (p < 0.05). Conversely, HFàLF reduced body weight and circulating hormones (leptin, resistin, and PAI-1) versus HF and HFàHFB (p < 0.05); however, AT inflammation and intestinal health markers were not improved to the same degree as HFàHFB (p < 0.05). Despite remaining on a HF obesogenic diet, introducing beans in established obesity improved the obese phenotype (intestinal health and adipose inflammation) more substantially than weight loss alone.


1998 ◽  
Vol 274 (6) ◽  
pp. R1536-R1545 ◽  
Author(s):  
John M. Bassett ◽  
Clifford Hanson

To evaluate contributions of catecholamines to inhibition of growth during chronic hypoxemia or severe undernutrition, epinephrine (Epi; 0.25–0.35 μg ⋅ kg−1 ⋅ min−1) or norepinephrine (NE; 0.5–0.7 μg ⋅ kg−1 ⋅ min−1) was administered to normoxemic fetuses in twin-pregnant ewes for 8–12 days, from 125 to 127 days of gestation. Both had similar effects and decreased fetal weight by ∼20% relative to control twins ( P < 0.01). Weight gain ceased during infusion of Epi or NE (−21 ± 14.8 or 14 ± 20.9 g/day), whereas controls gained 93 ± 13.2 g/day ( P < 0.01). Effects on tissues and organs varied, spleen and thymus being most retarded, whereas brain weight and skeletal measures were affected little. Selected muscles from infused fetuses weighed 72% of those in controls. Growth ceased during infusion ( P < 0.001). Weight gain of hindlimb bones was negligible, but length increased at 56% of control rates. Arterial blood CO2and plasma insulin were decreased ( P< 0.001), but plasma glucose, growth hormone, and blood oxygenation increased ( P < 0.001). Actions of Epi and NE could underlie asymmetrical growth retardation occurring in many adverse physiological situations during fetal development.


2009 ◽  
Vol 201 (3) ◽  
pp. 377-386 ◽  
Author(s):  
Lars P Klieverik ◽  
Ewout Foppen ◽  
Mariëtte T Ackermans ◽  
Mireille J Serlie ◽  
Hans P Sauerwein ◽  
...  

Thyronamines are naturally occurring, chemical relatives of thyroid hormone. Systemic administration of synthetic 3-iodothyronamine (T1AM) and – to a lesser extent – thyronamine (T0AM), leads to acute bradycardia, hypothermia, decreased metabolic rate, and hyperglycemia. This profile led us to hypothesize that the central nervous system is among the principal targets of thyronamines. We investigated whether a low dose i.c.v. infusion of synthetic thyronamines recapitulates the changes in glucose metabolism that occur following i.p. thyronamine administration. Plasma glucose, glucoregulatory hormones, and endogenous glucose production (EGP) using stable isotope dilution were monitored in rats before and 120 min after an i.p. (50 mg/kg) or i.c.v. (0.5 mg/kg) bolus infusion of T1AM, T0AM, or vehicle. To identify the peripheral effects of centrally administered thyronamines, drug-naive rats were also infused intravenously with low dose (0.5 mg/kg) thyronamines. Systemic T1AM rapidly increased EGP and plasma glucose, increased plasma glucagon, and corticosterone, but failed to change plasma insulin. Compared with i.p.-administered T1AM, a 100-fold lower dose administered centrally induced a more pronounced acute EGP increase and hyperglucagonemia while plasma insulin tended to decrease. Both systemic and central infusions of T0AM caused smaller increases in EGP, plasma glucose, and glucagon compared with T1AM. Neither T1AM nor T0AM influenced any of these parameters upon low dose i.v. administration. We conclude that central administration of low-dose thyronamines suffices to induce the acute alterations in glucoregulatory hormones and glucose metabolism following systemic thyronamine infusion. Our data indicate that thyronamines can act centrally to modulate glucose metabolism.


2019 ◽  
Vol 10 ◽  
Author(s):  
Dominika Stygar ◽  
Dorian Andrare ◽  
Barbara Bażanów ◽  
Elżbieta Chełmecka ◽  
Tomasz Sawczyn ◽  
...  

2008 ◽  
Vol 199 (6) ◽  
pp. S122
Author(s):  
Scott Petersen ◽  
Ronald Peeters ◽  
Frederik De Keyzer ◽  
Jan Deprest ◽  
Filip Claus

2013 ◽  
Vol 4 (2) ◽  
pp. 146-156 ◽  
Author(s):  
S. Li ◽  
D. M. Sloboda ◽  
T. J. M. Moss ◽  
I. Nitsos ◽  
G. R. Polglase ◽  
...  

Antenatal corticosteroids are used to augment fetal lung maturity in human pregnancy. Dexamethasone (DEX) is also used to treat congenital adrenal hyperplasia of the fetus in early pregnancy. We previously reported effects of synthetic corticosteroids given to sheep in early or late gestation on pregnancy length and fetal cortisol levels and glucocorticoids alter plasma insulin-like growth factor (IGF) and insulin-like growth factor binding protein (IGFBP) concentrations in late pregnancy and reduce fetal weight. The effects of administering DEX in early pregnancy on fetal organ weights and betamethasone (BET) given in late gestation on weights of fetal brain regions or organ development have not been reported. We hypothesized that BET or DEX administration at either stage of pregnancy would have deleterious effects on fetal development and associated hormones. In early pregnancy, DEX was administered as four injections at 12-hourly intervals over 48 h commencing at 40–42 days of gestation (dG). There was no consistent effect on fetal weight, or individual fetal organ weights, except in females at 7 months postnatal age. When BET was administered at 104, 111 and 118 dG, the previously reported reduction in total fetal weight was associated with significant reductions in weights of fetal brain, cerebellum, heart, kidney and liver. Fetal plasma insulin, leptin and triiodothyronine were also reduced at different times in fetal and postnatal life. We conclude that at the amounts given, the sheep fetus is sensitive to maternal administration of synthetic glucocorticoid in late gestation, with effects on growth and metabolic hormones that may persist into postnatal life.


Placenta ◽  
2014 ◽  
Vol 35 (9) ◽  
pp. A29
Author(s):  
Delphine Rousseau-Ralliard ◽  
Emilie Derisoud ◽  
Anne Tarrade ◽  
Roselyne Brat ◽  
Audrey Rolland ◽  
...  

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