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      In utero fuel homeostasis: Lessons for a clinician

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          Abstract

          Fetus exists in a complex, dynamic, and yet intriguing symbiosis with its mother as far as fuel metabolism is concerned. Though the dependence on maternal fuel is nearly complete to cater for its high requirement, the fetus is capable of some metabolism of its own. The first half of gestation is a period of maternal anabolism and storage whereas the second half results in exponential fetal growth where maternal stores are mobilized. Glucose is the primary substrate for energy production in the fetus though capable of utilizing alternate sources like lactate, ketoacids, amino acids, fatty acids, and glycogen as fuel under special circumstances. Key transporters like glucose transporters (GLUT) are responsible for preferential transfers, which are in turn regulated by complex interaction of maternal and fetal hormones. Amino acids are preferentially utilized for growth and essential fatty acids for development of brain and retina. Insulin, insulin like growth factors, glucagon, catecholamines, and letpin are the hormones implicated in this fascinating process. Hormonal regulation of metabolic substrate utilization and anabolism in the fetus is secondary to the supply of nutrient substrates. The knowledge of fuel homeostasis is crucial for a clinician caring for pregnant women and neonates to manage disorders of metabolism (diabetes), growth (intrauterine growth restriction), and transitional adaptation (hypoglycemia).

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          Most cited references37

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          Glucose transporters in the 21st Century.

          The ability to take up and metabolize glucose at the cellular level is a property shared by the vast majority of existing organisms. Most mammalian cells import glucose by a process of facilitative diffusion mediated by members of the Glut (SLC2A) family of membrane transport proteins. Fourteen Glut proteins are expressed in the human and they include transporters for substrates other than glucose, including fructose, myoinositol, and urate. The primary physiological substrates for at least half of the 14 Glut proteins are either uncertain or unknown. The well-established glucose transporter isoforms, Gluts 1-4, are known to have distinct regulatory and/or kinetic properties that reflect their specific roles in cellular and whole body glucose homeostasis. Separate review articles on many of the Glut proteins have recently appeared in this journal. Here, we provide a very brief summary of the known properties of the 14 Glut proteins and suggest some avenues of future investigation in this area.
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            Growth in utero and serum cholesterol concentrations in adult life.

            To see whether reduced rates of fetal growth are related to raised serum cholesterol concentrations in adult life. Follow up study of men and women whose size at birth had been recorded. Jessop and Northern General Hospitals, Sheffield. 219 men and women born in the Jessop Hospital during 1939-40. Serum concentrations of total cholesterol, low density lipoprotein cholesterol, and apolipoprotein B. Men and women who had had a small abdominal circumference at birth had raised serum concentrations of total and low density lipoprotein cholesterol and apolipoprotein B. This was independent of the duration of gestation. Serum concentrations of total cholesterol fell by 0.25 mmol/l (95% confidence interval 0.09 to 0.42) with each 1 in (2.54 cm) increase in abdominal circumference. The corresponding figure for serum low density lipoprotein cholesterol was 0.26 mmol/l (0.11 to 0.42) and for serum apolipoprotein B 0.04 g/l (0.02 to 0.07). Small head and chest circumferences at birth and short length were each associated with raised serum low density lipoprotein cholesterol concentrations but the trends disappeared in a simultaneous regression with abdominal circumference at birth. The association between abdominal circumference at birth and low density lipoprotein cholesterol concentration was independent of social class, current body weight, cigarette smoking, and alcohol consumption. Raised serum cholesterol concentrations in adult life are associated with impaired growth during late gestation, when fetal undernutrition has a disproportionate effect on liver growth. Impaired liver growth may permanently alter low density lipoprotein cholesterol metabolism.
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              Is birth weight a risk factor for ischemic heart disease in later life?

              An inverse association between birth weight and ischemic heart disease (IHD) has been seen in observational studies. We wanted to determine the strength and consistency of the association between birth weight and subsequent IHD. We conducted a systematic review of observational studies. Seventeen published studies of birth weight and subsequent IHD were identified that included a total of 144,794 singletons. Relative risk estimates for the association between birth weight and IHD were available from 16 of these studies. Additional data from 2 unpublished studies of 3801 persons were also included. In total, the analyses included data from 18 studies on 4210 nonfatal and 3308 fatal IHD events in 147,009 persons. The mean weighted estimate for the association between birth weight and the combined outcome of nonfatal and fatal IHD was 0.84 (95% CI: 0.81, 0.88) per kilogram of birth weight (P<0.0001). No significant heterogeneity was observed between estimates in different studies (P=0.09), nor was there evidence of publication bias (P=0.3, Begg test). Neither restricting the analysis to fatal IHD events nor adjusting for socioeconomic status had any appreciable effect on the findings. These findings are consistent with a 1 kg higher birth weight being associated with a 10-20% lower risk of subsequent IHD. However, even if causal, interventions to increase birth weight are unlikely to reduce the incidence of IHD materially. Further studies are needed to determine whether the observed association reflects a stronger underlying association with a related exposure or is due (at least in part) to residual confounding.
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                Author and article information

                Journal
                Indian J Endocrinol Metab
                Indian J Endocrinol Metab
                IJEM
                Indian Journal of Endocrinology and Metabolism
                Medknow Publications & Media Pvt Ltd (India )
                2230-8210
                2230-9500
                Jan-Feb 2013
                : 17
                : 1
                : 60-68
                Affiliations
                [1] Department of Neonatology, St. John's Medical College Hospital, Bangalore, Karnataka, India
                Author notes
                Corresponding Author: Dr. P. N. Suman Rao, Department of Neonatology, St. John's Medical College Hospital, Indiranagar, Bangalore, Karnataka, India. E-mail: raosumanv@ 123456rediffmail.com
                Article
                IJEM-17-60
                10.4103/2230-8210.107851
                3659908
                23776854
                1728e1f4-0272-4968-a02c-97682b88c96d
                Copyright: © Indian Journal of Endocrinology and Metabolism

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Categories
                Review Article

                Endocrinology & Diabetes
                fetus,fuel,glucose,metabolism
                Endocrinology & Diabetes
                fetus, fuel, glucose, metabolism

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