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Nutrients Apr 2022This review addresses the fasting vs. re-feeding effects of retinoic acid (RA) biosynthesis and functions, and sexually dimorphic RA actions. It also discusses other... (Review)
Review
This review addresses the fasting vs. re-feeding effects of retinoic acid (RA) biosynthesis and functions, and sexually dimorphic RA actions. It also discusses other understudied topics essential for understanding RA activities-especially interactions with energy-balance-regulating hormones, including insulin and glucagon, and sex hormones. This report will introduce RA homeostasis and hormesis to provide context. Essential context also will encompass RA effects on adiposity, muscle function and pancreatic islet development and maintenance. These comments provide background for explaining interactions among insulin, glucagon and cortisol with RA homeostasis and function. One aim would clarify the often apparent RA contradictions related to pancreagenesis vs. pancreas hormone functions. The discussion also will explore the adverse effects of RA on estrogen action, in contrast to the enhancing effects of estrogen on RA action, the adverse effects of androgens on RA receptors, and the RA induction of androgen biosynthesis.
Topics: Estrogens; Glucagon; Insulin; Receptors, Retinoic Acid; Tretinoin
PubMed: 35458115
DOI: 10.3390/nu14081553 -
The Journal of Endocrinology Aug 2023Glucagon is the principal glucose-elevating hormone that forms the first-line defence against hypoglycaemia. Along with insulin, glucagon also plays a key role in... (Review)
Review
Glucagon is the principal glucose-elevating hormone that forms the first-line defence against hypoglycaemia. Along with insulin, glucagon also plays a key role in maintaining systemic glucose homeostasis. The cells that secrete glucagon, pancreatic α-cells, are electrically excitable cells and use electrical activity to couple its hormone secretion to changes in ambient glucose levels. Exactly how glucose regulates α-cells has been a topic of debate for decades but it is clear that electrical signals generated by the cells play an important role in glucagon secretory response. Decades of studies have already revealed the key players involved in the generation of these electrical signals and possible mechanisms controlling them to tune glucagon release. This has offered the opportunity to fully understand the enigmatic α-cell physiology. In this review, we describe the current knowledge on cellular electrophysiology and factors regulating excitability, glucose sensing, and glucagon secretion. We also discuss α-cell pathophysiology and the perspective of addressing glucagon secretory defects in diabetes for developing better diabetes treatment, which bears the hope of eliminating hypoglycaemia as a clinical problem in diabetes care.
Topics: Humans; Glucagon; Glucagon-Secreting Cells; Insulin; Glucose; Diabetes Mellitus; Hypoglycemia; Cell Physiological Phenomena; Electrophysiology
PubMed: 37159865
DOI: 10.1530/JOE-22-0295 -
Pancreatology : Official Journal of the... 2017While the close morphological relationship between the exocrine and endocrine pancreas is well established, their functional interaction remains poorly understood. The...
BACKGROUND
While the close morphological relationship between the exocrine and endocrine pancreas is well established, their functional interaction remains poorly understood. The aim of this study was to investigate the associations between circulating levels of pancreatic proteolytic enzymes and insulin, as well as other pancreatic hormones.
METHODS
Fasting venous blood samples were collected and analyzed for trypsin, chymotrypsin, insulin, glucagon, somatostatin, and pancreatic polypeptide. Linear regression analysis was used in unadjusted and two adjusted (accounting for prediabetes/diabetes, body mass index, smoking, and other covariates) statistical models.
RESULTS
A total of 93 individuals with a history of acute pancreatitis were included in this cross-sectional study. Chymotrypsin was significantly associated with insulin in the two adjusted models (p = 0.005; p = 0.003) and just missed statistical significance in the unadjusted model (p = 0.066). Chymotrypsin was significantly associated with glucagon in both unadjusted (p = 0.025) and adjusted models (p = 0.014; p = 0.015); as well as with somatostatin - in both unadjusted (p = 0.001) and adjusted models (p = 0.001; p = 0.002). Trypsin was not significantly associated with insulin in any of the models but was significantly associated with glucagon in both unadjusted (p < 0.001) and adjusted models (p < 0.001), and pancreatic polypeptide in both unadjusted (p < 0.001) and adjusted (p < 0.001) models.
CONCLUSION
The state of hyperinsulinemia is characterized by a dysfunction of the exocrine pancreas. In particular, chymotrypsin is increased in the state of hyperinsulinemia and trypsin is significantly associated with glucagon and pancreatic polypeptide.
Topics: Adult; Aged; Chymotrypsin; Cross-Sectional Studies; Diabetes Mellitus; Female; Humans; Hyperinsulinism; Insulin; Male; Middle Aged; Pancreas; Pancreatitis; Trypsin
PubMed: 28958690
DOI: 10.1016/j.pan.2017.09.007 -
The Journal of Clinical Endocrinology... Jun 2022The bitter substance quinine modulates the release of a number of gut and gluco-regulatory hormones and upper gut motility. As the density of bitter receptors may be... (Randomized Controlled Trial)
Randomized Controlled Trial
CONTEXT
The bitter substance quinine modulates the release of a number of gut and gluco-regulatory hormones and upper gut motility. As the density of bitter receptors may be higher in the duodenum than the stomach, direct delivery to the duodenum may be more potent in stimulating these functions. The gastrointestinal responses to bitter compounds may also be modified by sex.
BACKGROUND
We have characterized the effects of intragastric (IG) versus intraduodenal (ID) administration of quinine hydrochloride (QHCl) on gut and pancreatic hormones and antropyloroduodenal pressures in healthy men and women.
METHODS
14 men (26 ± 2 years, BMI: 22.2 ± 0.5 kg/m2) and 14 women (28 ± 2 years, BMI: 22.5 ± 0.5 kg/m2) received 600 mg QHCl on 2 separate occasions, IG or ID as a 10-mL bolus, in randomized, double-blind fashion. Plasma ghrelin, cholecystokinin, peptide YY, glucagon-like peptide-1 (GLP-1), insulin, glucagon, and glucose concentrations and antropyloroduodenal pressures were measured at baseline and for 120 minutes following QHCl.
RESULTS
Suppression of ghrelin (P = 0.006), stimulation of cholecystokinin (P = 0.030), peptide YY (P = 0.017), GLP-1 (P = 0.034), insulin (P = 0.024), glucagon (P = 0.030), and pyloric pressures (P = 0.050), and lowering of glucose (P = 0.001) were greater after ID-QHCl than IG-QHCl. Insulin stimulation (P = 0.021) and glucose reduction (P = 0.001) were greater in females than males, while no sex-associated effects were found for cholecystokinin, peptide YY, GLP-1, glucagon, or pyloric pressures.
CONCLUSION
ID quinine has greater effects on plasma gut and pancreatic hormones and pyloric pressures than IG quinine in healthy subjects, consistent with the concept that stimulation of small intestinal bitter receptors is critical to these responses. Both insulin stimulation and glucose lowering were sex-dependent.
Topics: Cholecystokinin; Double-Blind Method; Energy Intake; Female; Gastrointestinal Motility; Ghrelin; Glucagon; Glucagon-Like Peptide 1; Glucose; Humans; Insulin; Male; Pancreatic Hormones; Peptide YY; Quinine
PubMed: 35325161
DOI: 10.1210/clinem/dgac182 -
Canadian Medical Association Journal Feb 1980Gastrointestinal endocrinology is the study of the hormonal regulation of digestion. A number of characterized polypeptide hormones have been localized in specific... (Review)
Review
Gastrointestinal endocrinology is the study of the hormonal regulation of digestion. A number of characterized polypeptide hormones have been localized in specific gastroenteropancreatic endocrine cells. The fact that some of these hormones are also found in nerve and brain cells has given rise to the concept of a gut-brain axis. The functional capacities of these endocrine cells are determined by their anatomic location; the luminal exposure of gastroenteric endocrine cells represents an additional avenue for stimulation and release that is not open to pancreatic endocrine cells. Gastroenteropancreatic hormones regulate carbohydrate metabolism, gastric acid secretion, pancreatic exocrine and gallbladder function, gastrointestinal motility and blood flow. These important regulatory hormones may in turn be controlled by a series of gastroduodenal releasing hormones.Diabetes mellitus is the most important metabolic disorder related to a gastroenteropancreatic hormone imbalance. Most tumours producing these hormones are of pancreatic origin and produce a number of hormones; insulinomas and gastrinomas are detected readily because of the serious metabolic distrubances they cause. Other instances of altered circulating concentrations of these hormones result from rather than cause the disease.The challenge of future study is to determine if postprandial changes in the plasma concentrations of these hormones are sufficient or necessary, or both, for the control of digestion.
Topics: Carbohydrate Metabolism; Diabetes Mellitus; Diarrhea; Digestion; Digestive System; Gastric Juice; Gastrointestinal Hormones; Humans; Pancreas; Pancreatic Hormones; Pancreatic Neoplasms; Syndrome
PubMed: 6989456
DOI: No ID Found -
International Journal of Molecular... Dec 2016The physiopathology of fatty liver and metabolic syndrome are influenced by diet, life style and inflammation, which have a major impact on the severity of the... (Review)
Review
The physiopathology of fatty liver and metabolic syndrome are influenced by diet, life style and inflammation, which have a major impact on the severity of the clinicopathologic outcome of non-alcoholic fatty liver disease. A short comprehensive review is provided on current knowledge of the pathophysiological interplay among major circulating effectors/mediators of fatty liver, such as circulating lipids, mediators released by adipose, muscle and liver tissues and pancreatic and gut hormones in relation to diet, exercise and inflammation.
Topics: Adipose Tissue; Gastrointestinal Hormones; Humans; Lipids; Muscles; Non-alcoholic Fatty Liver Disease; Pancreatic Hormones
PubMed: 27973438
DOI: 10.3390/ijms17122082 -
American Journal of Physiology.... Jul 2016Abnormal glucose metabolism is present in almost 40% of patients after acute pancreatitis, but its pathophysiology has been poorly investigated. Pancreatic hormone...
Abnormal glucose metabolism is present in almost 40% of patients after acute pancreatitis, but its pathophysiology has been poorly investigated. Pancreatic hormone derangements have been sparingly studied to date, and their relationship with abnormal glucose metabolism is largely unknown. The aim was to investigate the associations between pancreatic hormones and glucose metabolism after acute pancreatitis, including the effect of potential confounders. This was a cross-sectional study of 83 adult patients after acute pancreatitis. Fasting venous blood was collected from all patients and used for analysis of insulin, glucagon, pancreatic polypeptide, amylin, somatostatin, C-peptide, glucose, and hemoglobin A1c. Statistical analyses were conducted using the modified Poisson regression, multivariable linear regression, and Spearman's correlation. Age, sex, body mass index, recurrence of acute pancreatitis, duration from first attack, severity, and etiology were adjusted for. Increased insulin was significantly associated with abnormal glucose metabolism after acute pancreatitis, in both unadjusted (P = 0.038) and adjusted (P = 0.001) analyses. Patients with abnormal glucose metabolism also had significantly decreased pancreatic polypeptide (P = 0.001) and increased amylin (P = 0.047) in adjusted analyses. Somatostatin, C-peptide, and glucagon were not changed significantly in both unadjusted and adjusted analyses. Increased insulin resistance and reduced insulin clearance may be important components of hyperinsulinemic compensation in patients after acute pancreatitis. Increased amylin and reduced pancreatic polypeptide fasting levels characterize impaired glucose homeostasis. Clinical studies investigating islet-cell hormonal responses to mixed-nutrient meal testing and euglycemic-hyperinsulinemic clamps are now warranted for further insights into the role of pancreatic hormones in glucose metabolism derangements secondary to pancreatic diseases.
Topics: Acute Disease; Adult; Aged; Biomarkers; Blood Glucose; Chi-Square Distribution; Cross-Sectional Studies; Fasting; Female; Glucagon; Glycated Hemoglobin; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Islet Amyloid Polypeptide; Linear Models; Male; Middle Aged; Multivariate Analysis; Pancreatic Hormones; Pancreatic Polypeptide; Pancreatitis; Somatostatin
PubMed: 27173509
DOI: 10.1152/ajpgi.00074.2016 -
Islets Dec 2023Pancreatic islets are mini-organs composed of hundreds or thousands of ɑ, β and δ-cells, which, respectively, secrete glucagon, insulin and somatostatin, key hormones... (Review)
Review
Pancreatic islets are mini-organs composed of hundreds or thousands of ɑ, β and δ-cells, which, respectively, secrete glucagon, insulin and somatostatin, key hormones for the regulation of blood glucose. In pancreatic islets, hormone secretion is tightly regulated by both internal and external mechanisms, including electrical communication and paracrine signaling between islet cells. Given its complexity, the experimental study of pancreatic islets has been complemented with computational modeling as a tool to gain a better understanding about how all the mechanisms involved at different levels of organization interact. In this review, we describe how multicellular models of pancreatic cells have evolved from the early models of electrically coupled β-cells to models in which experimentally derived architectures and both electrical and paracrine signals have been considered.
Topics: Islets of Langerhans; Insulin-Secreting Cells; Insulin; Glucagon; Pancreatic Hormones
PubMed: 37415423
DOI: 10.1080/19382014.2023.2231609 -
American Journal of Physiology.... Jul 2010Although the role of the islets in the regulation of acinar cell function seemed a mystery to investigators who observed their dispersion among pancreatic acini, over... (Review)
Review
Although the role of the islets in the regulation of acinar cell function seemed a mystery to investigators who observed their dispersion among pancreatic acini, over time an appreciation for this intricate and unique structural arrangement has developed. The last three decades have witnessed a steadily growing understanding of the interrelationship of the endocrine and the exocrine pancreas. The islet innervation and vascular anatomy have been more fully characterized and provide an appropriate background for our current understanding. The interrelationship between the endocrine and exocrine pancreas is mediated by islet-derived hormones such as insulin and somatostatin, other humoral factors including pancreastatin and ghrelin, and also neurotransmitters (nitric oxide, peptide YY, substance P, and galanin) released by the nerves innervating the pancreas. Although considerable progress has been achieved, further work is required to fully delineate the complex interplay of the numerous mechanisms involved. This review aims to provide a comprehensive update of the current literature available, bringing together data gleaned from studies addressing the actions of individual hormones, humoral factors, and neurotransmitters on the regulation of amylase secretion from the acinar cell. This comprehensive view of the islet-acinar axis of the pancreas while acknowledging the dominant role played by insulin and somatostatin on exocrine secretion sheds light on the influence of the various neuropeptides on amylase secretion.
Topics: Amylases; Angiotensin II; Animals; Humans; Insulin; Islets of Langerhans; Neuropeptides; Pancreas, Exocrine; Pancreatic Hormones; Renin-Angiotensin System; Signal Transduction
PubMed: 20395539
DOI: 10.1152/ajpgi.00077.2010 -
Surgery For Obesity and Related... 2014Changes in the multiple mechanisms that regulate glucose metabolism after gastric bypass (RYGB) are still being unveiled. The objective of this study was to compare the... (Comparative Study)
Comparative Study
BACKGROUND
Changes in the multiple mechanisms that regulate glucose metabolism after gastric bypass (RYGB) are still being unveiled. The objective of this study was to compare the changes of glucose and pancreatic hormones [C-peptide, glucagon, and pancreatic polypeptide (PP)] during a meal tolerance test (MTT) and steady-state insulin and free fatty acid (FFA) concentrations during euglycemic-hyperinsulinemic clamp 14 days and 6 months after RYGB in morbidly obese nondiabetic patients.
METHODS
Two groups were studied at baseline and at 14 days: the RYGB followed by caloric restriction group (RYGB, n = 12) and the equivalent caloric restriction alone group (Diet, n = 10), to control for energy intake and weight loss. The RYGB group was studied again at 6 months to assess the changes after substantial weight loss. During MTT, the early and overall changes in glucose and pancreatic hormone concentrations were determined, and during the clamp, steady-state insulin and FFA concentrations were assessed.
RESULTS
After 14 days, RYGB patients had enhanced postprandial glucose, C-peptide, and glucagon responses, and decreased postprandial PP concentrations. Steady-state insulin concentrations were decreased at 14 days only in RYGB patients, and FFA increased in both groups. Six months after RYGB and substantial weight loss, the decrease in insulin concentrations during clamp persisted, and there were further changes in postprandial glucose and glucagon responses. FFA concentrations during clamp were significantly lower at 6 months, relative to presurgical values.
CONCLUSIONS
In morbidly obese nondiabetic patients, RYGB produces early changes in postmeal glucose, C-peptide, glucagon, and PP responses, and it appears to enhance insulin clearance early after RYGB and improve insulin sensitivity in adipose tissue at 6 months postsurgery. The early changes cannot be explained by caloric restriction alone.
Topics: Blood Glucose; Caloric Restriction; Fatty Acids, Nonesterified; Female; Follow-Up Studies; Gastric Bypass; Glucose Clamp Technique; Humans; Insulin; Male; Middle Aged; Obesity, Morbid; Pancreatic Hormones; Postoperative Care; Postprandial Period; Weight Loss
PubMed: 24209879
DOI: 10.1016/j.soard.2013.07.010