Newly discovered endocrine functions of the liver

The liver,the largest solid visceral organ of the body,has numerous endocrine functions,such as direct hormone and hepatokine production,hormone metabolism,synthesis of binding proteins,and processing and redistribution of metabolic fuels.In the last 10 years,many new endocrine functions of the liver have been discovered.Advances in the classical endocrine functions include delineation of mechanisms of liver production of endocrine hormones[including 25-hydroxyvitamin D,insulin-like growth factor 1(IGF-1),and angiotensinogen],hepatic metabolism of hormones(including thyroid hormones,glucagon-like peptide-1,and steroid hormones),and actions of specific binding proteins to glucocorticoids,sex steroids,and thyroid hormones.These studies have furthered insight into cirrhosis-associated endocrinopathies,such as hypogonadism,osteoporosis,IGF-1 deficiency,vitamin D deficiency,alterations in glucose and lipid homeostasis,and controversially relative adrenal insufficiency.Several novel endocrine functions of the liver have also been unraveled,elucidating the liver’s key negative feedback regulatory role in the pancreaticαcell-liver axis,which regulates pancreaticαcell mass,glucagon secretion,and circulating amino acid levels.Betatrophin and other hepatokines,such as fetuin-A and fibroblast growth factor 21,have also been discovered to play important endocrine roles in modulating insulin sensitivity,lipid metabolism,and body weight.It is expected that more endocrine functions of the liver will be revealed in the near future.

Impacts of prenatal nutrition on animal production and performance： a focus on growth and metabolic and endocrine function in sheep

The concept of foetal programming（FP） originated from human epidemiological studies, where foetal life nutrition was linked to health and disease status later in life. Since the proposal of this phenomenon, it has been evaluated in various animal models to gain further insights into the mechanisms underlying the foetal origins of health and disease in humans. In FP research, the sheep has been quite extensively used as a model for humans. In this paper we will review findings mainly from our Copenhagen sheep model, on the implications of late gestation malnutrition for growth, development, and metabolic and endocrine functions later in life, and discuss how these implications may depend on the diet fed to the animal in early postnatal life. Our results have indicated that negative implications of foetal malnutrition, both as a result of overnutrition and, particularly, late gestation undernutrition, can impair a wide range of endocrine functions regulating growth and presumably also reproductive traits. These implications are not readily observable early in postnatal life, but are increasingly manifested as the animal approaches adulthood. No intervention or cure is known that can reverse this programming in postnatal life. Our findings suggest that close to normal growth and slaughter results can be obtained at least until puberty in animals which have undergone adverse programming in foetal life, but manifestation of programming effects becomes increasingly evident in adult animals.Due to the risk of transfer of the adverse programming effects to future generations, it is therefore recommended that animals that are suspected to have undergone adverse FP are not used for reproduction. Unfortunately, no reliable biomarkers have as yet been identified that allow accurate identification of adversely programmed offspring at birth,except for very low or high birth weights, and, in pigs, characteristic changes in head shape（dolphin head）. Future efforts should be therefore dedicated to identify reliable biomarkers and evaluate their effectiveness for alleviation/reversal of the adverse programming in postnatal life. Our sheep studies have shown that the adverse impacts of an extreme, high-fat diet in early postnatal life, but not prenatal undernutrition, can be largely reversed by dietary correction later in life. Thus, birth（at term） appears to be a critical set point for permanent programming in animals born precocial,such as sheep. Appropriate attention to the nutrition of the late pregnant dam should therefore be a priority in animal production systems.

A comparative study of pancreatic endocrine function and related metabolism after long-term survival between the patients with combined kidneypancreas transplantation vs those with combined en bloc ' liver-pancreas transplantation

Objective To compare the effects of combined en bloc liver - pancreas transplantation ( LPT) with portal vein drainage and simultaneous combined kidney - pancreas transplantation ( KPT) with systemic venous drainage on the pancreatic endocrine function and related me-

Exercise-Dependent Modulation of Bone Metabolism and Bone Endocrine Function:New Findings and Therapeutic Perspectives

Physical inactivity is the fourth leading cause of mortality worldwide;regardless of geographic location and income,it is a contributing risk factor to the other three causes.Physical activity is really a drug,a poly-pill;its“regular use”can reduce this risk throughout the activation of a plethora of responses in virtually all the body tissues.The beneficial effects of physi-cal activity on cardiovascular function and hemodynamics are mainly mediated by skeletal muscle,adipose tissue and the immune system via the usage,delivery and distribution of metabolic substrates and improvement in inflammatory status.There is emerging evidence for exercise-dependent changes in bone metabolism as well;with improved bone quality,reduced fracture risk and increased bone endocrine function,the last of which modulates energy metabolism through its effects on pancreatic islet cells,skeletal muscle and adipose tissue.Bone endocrine function relies on the integration of biomechani-cal stimuli and endocrine signals from other organs and tissues.Here I review current concepts about exercise-dependent modulation of bone endocrine function and its beneficial effects on whole-body metabolism.Several molecular mechanisms have been identified that support this exercise-stimulated bone-mediated metabolic effect and,among these,Wnt signaling,fibroblast growth factor-23,bone morphogenic protein-7,osteocalcin,RANK/RANKL/OPG axis,and lipocalin-2 gave the largest evidences.In conclusion,beside the controversies surrounding technical aspects of the exercise,the efficacy of physi-cal activity in preventing/treating metabolic and inflammatory dysfunctions also passes throughout the bone.

Pancreatic necrosis and severity are independent risk factors for pancreatic endocrine insufficiency after acute pancreatitis: A long-term follow-up study

BACKGROUND Pancreatic endocrine insufficiency after acute pancreatitis(AP) has drawn increasing attention in recent years.AIM To assess the impact of risk factors on the development of pancreatic endocrine insufficiency after AP.METHODS This retrospective observational long-term follow-up study was conducted in a tertiary hospital. Endocrine function was evaluated by the oral glucose tolerance test. The data, including age, sex, body mass index, APACHE II score, history of smoking and drinking, organ failure, pancreatic necrosis, debridement of necrosis(minimally invasive and/or open surgery), and time interval, were collected from the record database.RESULTS A total of 361 patients were included in the study from January 1, 2012 to December 30, 2018. A total of 150(41.6%) patients were diagnosed with dysglycemia(including diabetes mellitus and impaired glucose tolerance), while211(58.4%) patients had normal endocrine function. The time intervals(mo) of the above two groups were 18.73 ± 19.10 mo and 31.53 ± 27.27 mo, respectively(P= 0.001). The morbidity rates of pancreatic endocrine insufficiency were 46.7%,28.0%, and 25.3%, respectively, in the groups with different follow-up times. The risk factors for pancreatic endocrine insufficiency after AP were severity(odds ratio [OR] = 3.489;95% confidence interval [CI]: 1.501-8.111;P = 0.004) and pancreatic necrosis(OR = 4.152;95%CI: 2.580-6.684;P = 0.001).CONCLUSION Pancreatic necrosis and severity are independent risk factors for pancreatic endocrine insufficiency after AP. The area of pancreatic necrosis can affect pancreatic endocrine function.

Bone functions as a novel endocrine organ in energy metabolism

The classic endocrine concept is a matter of dispute. The term ＂endocrine＂ denotes internal secretion of bioactive substances, in contrast to ＂exocrine,＂ which denotes secretion outside the body. Traditionally, the endocrine organs refer to classic organs, such as the thyroid, gonadal, or adrenal glands; however, some non-classic endocrine organs have been shown to have endocrine functions. For example,

Central pancreatectomy for benign or low-grade malignant pancreatic tumors in the neck and body of the pancreas

BACKGROUND For tumors in the neck and body of the pancreas,distal pancreatectomy(DP)has been the standard surgical procedure for the last few decades and central pancreatectomy(CP)is an alternative surgical option.Whether CP better preserves remnant pancreatic endocrine and exocrine functions after surgery remains a subject of debate.AIM To evaluate the safety and efficacy of CP compared with DP for benign or lowgrade malignant pancreatic tumors in the neck and body of the pancreas.METHODS This retrospective study enrolled 296 patients who underwent CP or DP for benign and low-malignant neoplasms at the same hospital between January 2016 and March 2020.Perioperative outcomes and long-term morbidity of endocrine/exocrine function were prospectively evaluated.RESULTS No significant difference was observed in overall morbidity or clinically relevant postoperative pancreatic fistula between the two groups(P=0.055).Delayed gastric emptying occurred more frequently in the CP group than in the DP group(29.4%vs 15.3%;P<0.005).None of the patients in the CP group had new-onset or aggravated distal metastasis,whereas 40 patients in the DP group had endocrine function deficiency after surgery(P<0.05).There was no significant difference in the incidence of diarrhea immediately after surgery,but at postoperative 12 mo,a significantly higher number of patients had diarrhea in the DP group than in the CP group(0%vs 9.5%;P<0.05).CONCLUSION CP is a generally safe procedure and is better than DP in preserving long-term pancreatic endocrine and exocrine functions.Therefore,CP might be a better option for treating benign or low-grade malignant neoplasms in suitable patients.

Organophosphate esters cause thyroid dysfunction via multiple signaling pathways in zebrafish brain

Organophosphate esters(OPEs)are widespread in various environmental media,and can disrupt thyroid endocrine signaling pathways.Mechanisms by which OPEs disrupt thyroid hormone(TH)signal transduction are not fully understood.Here,we present in vivo-in vitro-in silico evidence establishing OPEs as environmental THs competitively entering the brain to inhibit growth of zebrafish via multiple signaling pathways.OPEs can bind to transthyretin(TTR)and thyroxine-binding globulin,thereby affecting the transport of TH in the blood,and to the brain by TTR through the blood-brain barrier.When GH3 cells were exposed to OPEs,cell proliferation was significantly inhibited given that OPEs are competitive inhibitors of TH.Cresyl diphenyl phosphate was shown to be an effective antagonist of TH.Chronic exposure to OPEs significantly inhibited the growth of zebrafish by interfering with thyroperoxidase and thyroglobulin to inhibit TH synthesis.Based on comparisons of modulations of gene expression with the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases,signaling pathways related to thyroid endocrine functions,such as receptor-ligand binding and regulation of hormone levels,were identified as being affected by exposure to OPEs.Effects were also associated with the biosynthesis and metabolism of lipids,and neuroactive ligand-receptor interactions.These findings provide a comprehensive understanding of the mechanisms by which OPEs disrupt thyroid pathways in zebrafish.

Clinical Observation on the Endocrinal and Immune Functions in Subjects with Yin-deficiency Constitution

Objective： To explore the relationship between yin-deficiency constitution （YDC） and biochemical indexes by way of observing the endocrinal and immune functions in subjects with YDC. Methods： On the basis of epidemiological investigation, 60 subjects with YDC and 50 with gentle constitution （GC） were selected according to the pertinent criteria. From each subject, 8 mL of fasting venous blood was drawn at 8：00-9：00 in the morning, with the serum separated by centrifugation 3 000 r/min for 5 min and preserved at -70℃ in a freezer. Serum levels of corticosterone, cortisol, adrenocorticotrophic hormone （ACTH）, cyclic adenosine monophosphate （cAMP）, cyclic guanosine monophosphate （cGMP）, free triiodothyronine （FT3）, free thyroxine （1=-1-4）, throtropic stimulation hormone, interleukin 1β （IL-1β ） and interleukin 2 （IL-2） were detected by doubleantibody sandwich ELISA; cAMP/cGMP ratio was calculated, and the difference between the two constitutions in terms of these indexes was analyzed. Results： Serum FT3 was 4.16 ± 1.38 pmol/L in subjects with YDC, which was higher than that in subjects with GC （3.71 ±0.55 pmol/L）, but levels of cortisol （124.58± 45.36 ng/mL）, ACTH （58.92± 14.55 pg/mL）, cGMP （66.00 ± 18.02 pmol/mL） and FT4 （12.33 ± 3.12 pmol/L） in YDC were lower than those in GC （13.43±2.31 pmol/L）, showing significant difference （P〈0.05）. Conclusion： YDC is related to some extent with the disturbances in the hypothalamus-pituitary-adrenal axis, hypothalamus-pituitary-thyroid axis, cyclic nucleoside system and immune function.