Prolonged Prepregnant Maternal High-Fat Feeding Reduces Fetal and Neonatal Blood Glucose Concentrations by Enhancing Fetal β-cell Development in C57BL/6 Mice

High-fat feeding reduces the expression of GLUT-2 and the glycolytic enzyme glucokinase (GK). The transcription factor, pancreatic duodenal homeobox-1 (Pdx-1), is important for β-cell maintenance. The aim of the present study was to determine, in weanling Wistar rats, the effect of a maternal high-fat diet (HFD) during defined periods of gestation and lactation, on body weight, circulating glucose and insulin concentrations, and the expression of GLUT-2, GK and Pdx-1. At postnatal day 21, weights were recorded and glucose and insulin concentrations were measured. The expression levels for mRNA were quantified by LightCycler PCR. Pancreatic sections, immunostained for GLUT-2, GK or Pdx-1, were assessed by image analysis. Weanlings from dams fed an HFD throughout gestation were lighter, with heavier weanlings produced from dams fed an HFD throughout gestation and lactation. Both these groups of weanlings were normoglycaemic, all the others being hyperglycaemic. Hypoinsulinaemia was evident in weanlings from dams fed an HFD throughout gestation only and also for either the first week of lactation or throughout lactation. GLUT-2 mRNA expression was reduced and GLUT-2 immunoreactivity was increased in most of the weanlings. GK mRNA expression and immunoreactivity was reduced in most of the offspring. Pdx-1 mRNA expression was increased in weanlings from dams fed an HFD throughout both gestation and lactation and reduced in those from dams only fed a lactational HFD. Normal Pdx-1 immunoreactivity was found in all of the weanlings. A maternal HFD induces hyperglycaemia in weanlings concomitant with reduced GK expression which may compromise β-cell function.

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Short-term high-fat feeding induces islet macrophage infiltration and β-cell replication independently of insulin resistance in mice

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00092.2016 ◽

2016 ◽

Vol 311 (4) ◽

pp. E763-E771 ◽

Cited By ~ 5

Author(s):

David C. Woodland ◽

Wei Liu ◽

Jacky Leong ◽

Mallory L. Sears ◽

Ping Luo ◽

...

Keyword(s):

Insulin Resistance ◽

Blood Glucose ◽

Serum Insulin ◽

Cell Replication ◽

Fat Pad ◽

High Fat ◽

Fasting Serum ◽

Β Cell ◽

Short Term ◽

Insulin Levels

Short-term high-fat consumption stimulates mouse islet β-cell replication through unknown mechanisms. Resident macrophages (MΦs) are capable of secreting various factors involved in islet development and tissue remodeling. We hypothesized that a short-term high-fat diet (HFD) promotes MΦ infiltration in pancreatic islets and that MΦs serve as a regulator of β-cell replication. To test these hypotheses and dissect mechanisms involved in HFD-induced β-cell replication, adult C57BL/6J mice were fed a HFD for 7 days with or without administration of clodronate-containing liposomes, an MΦ-depleting agent. Mouse body and epididymal fat pad weights, and nonfasting blood glucose and fasting serum insulin levels were measured, and pancreatic islet β-cell replication, oxidative stress, and MΦ infiltration were examined. Short-term HFD promoted an increase in body and epididymal fat pad weight and blood glucose levels, along with an increased fasting serum insulin concentration. β-Cell replication, islet MΦ infiltration, and the percentage of inducible NO synthase positive MΦs in the islets increased significantly in mice fed the HFD. Immunofluorescence staining for 8-oxo-2′-deoxyguanosine or activated caspase-3 revealed no significant induction of DNA damage or apoptosis, respectively. In addition, no change in stromal-derived factor 1-expressing cells was found induced by HFD. Despite continuous elevation of nonfasting blood glucose and fasting serum insulin levels, depletion of MΦs through treatments of clodronate abrogated HFD-induced β-cell replication. These findings demonstrated that HFD-induced MΦ infiltration is responsible for β-cell replication. This study suggests the existence of MΦ-mediated mechanisms in β-cell replication that are independent of insulin resistance.

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F4-01-04: APOE GENOTYPE INFLUENCES BRAIN TO BLOOD GLUCOSE RATIOS AFTER HIGH FAT FEEDING

Alzheimer s & Dementia ◽

10.1016/j.jalz.2018.06.2867 ◽

2006 ◽

Vol 14 (7S_Part_26) ◽

pp. P1383-P1383

Author(s):

Angela J. Hanson ◽

Kelly C. Stewart ◽

Deepa Subramaniyan ◽

Suzanne Craft ◽

William A. Banks

Keyword(s):

Blood Glucose ◽

Apoe Genotype ◽

High Fat ◽

Fat Feeding

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Neonatal blood glucose concentrations in caesarean and vaginally delivered term infants

Yearbook of Neonatal and Perinatal Medicine ◽

10.1016/j.ynpm.2011.03.008 ◽

2011 ◽

Vol 2011 ◽

pp. 269-270

Author(s):

A.A. Fanaroff

Keyword(s):

Blood Glucose ◽

Term Infants ◽

Neonatal Blood ◽

Blood Glucose Concentrations

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Islet cell response in the neonatal rat after exposure to a high-fat diet during pregnancy

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00335.2004 ◽

2005 ◽

Vol 288 (5) ◽

pp. R1122-R1128 ◽

Cited By ~ 62

Author(s):

M. E. Cerf ◽

K. Williams ◽

X. I. Nkomo ◽

C. J. Muller ◽

D. F. Du Toit ◽

...

Keyword(s):

Cell Volume ◽

High Fat Diet ◽

Cell Mass ◽

Cell Development ◽

Neonatal Rat ◽

High Fat ◽

Β Cell ◽

Adult Rats ◽

Volume Number ◽

Insulin Requirements

Although pancreatic β-cells are capable of adapting their mass in response to insulin requirements, evidence has shown that a dietary insult could compromise this ability. Fetal malnutrition has been linked to low birth weight and the development of type 2 diabetes later in life, while reduced β-cell mass has been reported in adult rats fed a high-fat diet (HFD). Reported here are the effects of exposure to a HFD, during different periods of gestation, on neonatal rat weight and β- and α-cell development. The experimental groups were composed of neonatal offspring obtained from Wistar rats fed a high-fat (40% as energy) diet for either the first (HF1), second (HF2), or third (HF3) week, or all three (HF1–3) weeks of gestation. Neonatal weights and circulating glucose and insulin concentrations were measured on postnatal day 1, after which the pancreata were excised and processed for histological immunocytochemical examination and image analysis. HF1 and HF2 neonates were hypoglycemic, whereas HF1–3 neonates were hyperglycemic. Low birth weights were observed only in HF1 neonates. No significant differences were detected in the circulating insulin concentrations in the neonates, although β-cell volume and numbers were reduced in HF1–3 neonates. β-cell numbers also declined in HF1 and HF3 neonates. α-cell volume, number and size were, however, increased in HF1–3 neonates. α-cell size was also increased in HF1 and HF3 neonates. In neonates, exposure to a maternal HFD throughout gestation was found to have the most adverse effect on β-cell development and resulted in hyperglycemia.

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Early and rapid development of insulin resistance, islet dysfunction and glucose intolerance after high-fat feeding in mice overexpressing phosphodiesterase 3B

Journal of Endocrinology ◽

10.1677/joe.1.06522 ◽

2006 ◽

Vol 189 (3) ◽

pp. 629-641 ◽

Cited By ~ 19

Author(s):

Helena A Walz ◽

Linda Härndahl ◽

Nils Wierup ◽

Emilia Zmuda-Trzebiatowska ◽

Fredrik Svennelid ◽

...

Keyword(s):

Insulin Resistance ◽

Glucose Intolerance ◽

Rapid Development ◽

Control Diet ◽

Wild Type ◽

High Fat ◽

Β Cell ◽

Phosphodiesterase 3B ◽

Fat Feeding

Inadequate islet adaptation to insulin resistance leads to glucose intolerance and type 2 diabetes. Here we investigate whether β-cell cAMP is crucial for islet adaptation and prevention of glucose intolerance in mice. Mice with a β-cell-specific, 2-fold overexpression of the cAMP-degrading enzyme phosphodiesterase 3B (RIP-PDE3B/2 mice) were metabolically challenged with a high-fat diet. We found that RIP-PDE3B/2 mice early and rapidly develop glucose intolerance and insulin resistance, as compared with wild-type littermates, after 2 months of high-fat feeding. This was evident from advanced fasting hyperinsulinemia and early development of hyper-glycemia, in spite of hyperinsulinemia, as well as impaired capacity of insulin to suppress plasma glucose in an insulin tolerance test. In vitro analyses of insulin-stimulated lipogenesis in adipocytes and glucose uptake in skeletal muscle did not reveal reduced insulin sensitivity in these tissues. Significant steatosis was noted in livers from high-fat-fed wild-type and RIP-PDE3B/2 mice and liver triacyl-glycerol content was 3-fold higher than in wild-type mice fed a control diet. Histochemical analysis revealed severe islet perturbations, such as centrally located α-cells and reduced immunostaining for insulin and GLUT2 in islets from RIP-PDE3B/2 mice. Additionally, in vitro experiments revealed that the insulin secretory response to glucagon-like peptide-1 stimulation was markedly reduced in islets from high-fat-fed RIP-PDE3B/2 mice. We conclude that accurate regulation of β-cell cAMP is necessary for adequate islet adaptation to a perturbed metabolic environment and protective for the development of glucose intolerance and insulin resistance.

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Long-term high-fat feeding leads to severe insulin resistance but not diabetes in Wistar rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00173.2001 ◽

2002 ◽

Vol 282 (6) ◽

pp. E1231-E1238 ◽

Cited By ~ 73

Author(s):

Simon M. Chalkley ◽

Manthinda Hettiarachchi ◽

Donald J. Chisholm ◽

Edward W. Kraegen

Keyword(s):

Insulin Resistance ◽

Wistar Rats ◽

Cell Function ◽

Insulin Response ◽

High Fat ◽

Β Cell ◽

Intravenous Glucose ◽

Severe Insulin Resistance ◽

Fat Feeding

Although lipid excess can impair β-cell function in vitro, short-term high-fat feeding in normal rats produces insulin resistance but not hyperglycemia. This study examines the effect of long-term (10-mo) high polyunsaturated fat feeding on glucose tolerance in Wistar rats. The high fat-fed compared with the chow-fed group was 30% heavier and 60% fatter, with approximately doubled fasting hyperinsulinemia ( P < 0.001) but only marginal fasting hyperglycemia (7.5 ± 0.1 vs. 7.2 ± 0.1 mmol/l, P < 0.01). Insulin sensitivity was ∼67% lower in the high-fat group ( P < 0.01). The acute insulin response to intravenous arginine was approximately double in the insulin-resistant high-fat group ( P < 0.001), but that to intravenous glucose was similar in the two groups. After the intravenous glucose bolus, plasma glucose decline was slower in the high fat-fed group, confirming mild glucose intolerance. Therefore, despite severe insulin resistance, there was only a mildly elevated fasting glucose level and a relative deficiency in glucose-stimulated insulin secretion; this suggests that a genetic or congenital susceptibility to β-cell impairment is required for overt hyperglycemia to develop in the presence of severe insulin resistance.

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