scholarly journals Glucagon-Producing Cell Expansion in Wistar Rats. Changes to Islet Architecture After Sleeve Gastrectomy

2021 ◽  
Author(s):  
José Bancalero-delosReyes ◽  
Alonso Camacho-Ramírez ◽  
José Fernández-Vivero ◽  
Antonio Ribelles-García ◽  
Manuel Macías-Rodríguez ◽  
...  
Keyword(s):  
Sleeve Gastrectomy ◽  
Glucose Tolerance ◽  
Beta Cell ◽  
Cell Population ◽  
Wistar Rats ◽  
Insulin Infusion ◽  
Cell Mass ◽  
Glucagon Secretion ◽  
Alpha Cell ◽  
Plasma Glucagon

Abstract Purpose Many studies about bariatric surgery have analyzed the effect of sleeve gastrectomy (SG) on glucose improvement, beta-cell mass, and islet size modification. The effects of SG on the other endocrine cells of the pancreas, such as the alpha-cell population, and their regulatory mechanisms remain less studied. Materials and Methods We focused our work on the changes in the alpha-cell population after SG in a healthy model of Wistar rats. We measured alpha-cell mass, glucose tolerance, and insulin release after oral glucose tolerance tests and plasma glucagon secretion patterns after insulin infusion. Three Wistar rat groups were employed: SG-operated, surgical control (Sham), and fasting control. Results The results obtained showed significant increases in the alpha-cell population after SG. The result was an increase in beta-cell transdifferentiation; it was shown by some expressed molecules (the loss of expression of Pdx-1 and the increase in Arx and Pax6 cells/mm2 of islet). The serum results were enhanced plasma glucagon secretion pattern after insulin infusion assays and normal glucose tolerance and insulin release after OGTT. Conclusion We concluded that SG leads to an expansion of the alpha-cell population, at expense of beta-cell; this expansion of alpha-cells is related to transdifferentiation. Plasma glucose level was not affected due to an increased glucagon response.

scholarly journals Increased alpha and beta cell mass during mouse pregnancy is not dependent on transdifferentiation

2020 ◽  
pp. 153537022097268
Author(s):  
Sandra K Szlapinski ◽  
Jamie Bennett ◽  
Brenda J Strutt ◽  
David J Hill
Keyword(s):  
Beta Cell ◽  
Fluorescent Protein ◽  
Control Diet ◽  
Yellow Fluorescent Protein ◽  
Pancreatic Beta Cell ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Alpha Cell ◽  
Β Cell ◽  
Cell Conversion

Maternal pancreatic beta-cell mass (BCM) increases during pregnancy to compensate for relative insulin resistance. If BCM expansion is suboptimal, gestational diabetes mellitus can develop. Alpha-cell mass (ACM) also changes during pregnancy, but there is a lack of information about α-cell plasticity in pregnancy and whether α- to β-cell transdifferentiation can occur. To investigate this, we used a mouse model of gestational glucose intolerance induced by feeding low-protein (LP) diet from conception until weaning and compared pregnant female offspring to control diet-fed animals. Control and LP pancreata were collected for immunohistochemical analysis and serum glucagon levels were measured. In order to lineage trace α- to β-cell conversion, we utilized transgenic mice expressing yellow fluorescent protein behind the proglucagon gene promoter (Gcg-Cre/YFP) and collected pancreata for histology at various gestational timepoints. Alpha-cell proliferation increased significantly at gestational day (GD) 9.5 in control pregnancies resulting in an increased ACM at GD18.5, and this was significantly reduced in LP animals. Despite these changes, serum glucagon was higher in LP mice at GD18.5. Pregnant Gcg-Cre/YFP mice showed no increase in the abundance of insulin+YFP+glucagon– cells (phenotypic β-cells). A second population of insulin+YFP+glucagon+ cells was identified which also did not alter during pregnancy. However, there was an altered anatomical distribution within islets with fewer insulin+YFP+glucagon– cells but more insulin+YFP+glucagon+ cells being present in the islet mantle at GD18.5. These findings demonstrate that dynamic changes in ACM occur during normal pregnancy and were altered in glucose-intolerant pregnancies.

Sleeve gastrectomy, but not duodenojejunostomy, preserves total beta-cell mass in Goto-Kakizaki rats evaluated by three-dimensional optical projection tomography

2015 ◽  
Vol 30 (2) ◽  
pp. 532-542 ◽  
Author(s):  
Eivind Grong ◽  
Bård Kulseng ◽  
Ingerid Brænne Arbo ◽  
Christoffer Nord ◽  
Maria Eriksson ◽  
...  
Keyword(s):  
Sleeve Gastrectomy ◽  
Beta Cell ◽  
Cell Mass ◽  
Three Dimensional ◽  
Beta Cell Mass ◽  
Optical Projection Tomography ◽  
Optical Projection ◽  
Total Beta

Glucagon-like peptide-1: a major regulator of pancreatic beta-cell function

2000 ◽  
pp. 717-725 ◽  
Author(s):  
R Perfetti ◽  
P Merkel
Keyword(s):  
Beta Cell ◽  
Cell Function ◽  
Pancreatic Beta Cell ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Glucagon Secretion ◽  
Insulin Biosynthesis ◽  
Gut Hormone ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Glucagon-like peptide-1 (GLP-1) is a gut hormone synthesized by post-translational processing in intestinal L-cells, and it is released in response to food ingestion. GLP-1 stimulates insulin secretion during hyperglycemia, suppresses glucagon secretion, stimulates (pro)-insulin biosynthesis and decreases the rate of gastric emptying and acid secretion. GLP-1 has also been shown to have a pro-satiety effect. In addition, it has been demonstrated that a long-term infusion with GLP-1, or exendin-4, a long-acting analog of human GLP-1, increases beta-cell mass in rats. In conclusion, GLP-1 appears to regulate plasma glucose levels via various and independent mechanisms. GLP-1 is an excellent candidate option for the treatment of patients with type 2 diabetes mellitus.

scholarly journals Glucokinase Inactivation Paradoxically Ameliorates Glucose Intolerance by Increasing Beta-Cell Mass in db/db Mice

2021 ◽  
Author(s):  
Kazuno Omori ◽  
Akinobu Nakamura ◽  
Hideaki Miyoshi ◽  
Yuki Yamauchi ◽  
Shinichiro Kawata ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Beta Cell ◽  
Beta Cells ◽  
Beta Cell Function ◽  
Cell Function ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Glucose Signalling ◽  
Excess Glucose

Efficacy of glucokinase activation on glycemic control is limited to a short-term period. One reason might be related with the excess glucose signalling by glucokinase activation towards beta-cells. In this study, we investigated the effect of glucokinase haploinsufficiency on glucose tolerance as well as beta-cell function and mass using a mouse model of type 2 diabetes. Our results showed that <i>db/db</i> mice with glucokinase haploinsufficiency presented amelioration of glucose tolerance by augmented insulin secretion associated with the increase in beta-cell mass when compared with <i>db/db</i> mice. Gene expression profiling, and immunohistochemical and metabolomic analyses revealed that glucokinase haploinsufficiency in the islets of <i>db/db</i> mice was associated with lower expression of stress-related genes, higher expression of transcription factors involved in the maintenance and maturation of beta-cell function, less mitochondrial damage, and a superior metabolic pattern. These effects of glucokinase haploinsufficiency could preserve beta-cell mass under diabetic conditions. These findings verified our hypothesis that optimizing excess glucose signalling in beta-cells by inhibiting glucokinase could prevent beta-cell insufficiency, leading to improving glucose tolerance in diabetes status by preserving beta-cell mass. Therefore, glucokinase inactivation in beta-cells could, paradoxically, be a potential strategy for the treatment of type 2 diabetes.

scholarly journals BACE1, but not BACE2, function is critical for metabolic disorders induced by high-fat diets in C57BL/6N mice

2021 ◽  
Author(s):  
Thomas W Rosahl ◽  
Lynn A Hyde ◽  
Patrick T Reilly ◽  
Marie-France Champy ◽  
Kristin J Belongie ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Glucose Tolerance ◽  
Beta Cell ◽  
Pancreatic Beta Cells ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
High Fat ◽  
Modest Improvement ◽  
Peripheral Tissues

Beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1) is required for the production of toxic amyloid peptides and is highly expressed in the brain, but also to a lesser extent in major peripheral organs such as muscle and liver. In contrast, BACE2 is mainly expressed in peripheral tissues and is enriched in pancreatic beta cells, where it regulates beta-cell function and mass. Previous reports demonstrated that loss of BACE1 function decreases body weight, protects against diet-induced obesity and enhances insulin sensitivity in mice, whereas mice lacking Bace2 exhibit reduced blood glucose levels, improved intraperitoneal glucose tolerance and increased beta-cell mass. Impaired glucose homeostasis and insulin resistance are hallmarks of type 2 diabetes and have been implicated in Alzheimers disease. Therefore, we tested the contribution of the individual BACE isoforms to those metabolic phenotypes by placing Bace1 knockout (KO), Bace2 KO, Bace1/2 double knockout (dKO) and wild-type (WT) mice on a high-fat high-cholesterol diet (HFD) for 16 weeks. Bace1 KO and Bace1/2 dKO mice showed decreased body weight and improved glucose tolerance and insulin resistance vs. WT mice. Conversely, Bace2 KO mice did not show any significant differences in body weight, glucose tolerance or insulin resistance under our experimental conditions. Finally, subchronic MBi-3 mediated BACE1/2 inhibition in mice in conjunction with a HFD resulted in a modest improvement of glucose tolerance. Our data indicate that lack of BACE1, but not BACE2, function contributes mainly to the metabolic phenotypic changes observed in Bace1/2 dKO mice, suggesting that inhibition of BACE1 has the greater role (vs. BACE2) in any potential improvements in metabolic homeostasis.

scholarly journals Pancreatic alpha-cell mass across adult human lifespan

2020 ◽  
Vol 182 (2) ◽  
pp. 219-231 ◽  
Author(s):  
Abu Saleh Md Moin ◽  
Megan Cory ◽  
Tatyana Gurlo ◽  
Yoshifumi Saisho ◽  
Robert A Rizza ◽  
...  
Keyword(s):  
Beta Cell ◽  
Exocrine Pancreas ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Alpha Cell ◽  
Advanced Age ◽  
Alpha Cells ◽  
Adult Lifespan ◽  
Human Lifespan ◽  
Pancreatic Alpha Cell

Aim To establish pancreatic alpha-cell mass in lean, non-diabetic humans over the adult lifespan, performed as a follow-up study to beta-cell mass across the adult human lifespan. Methods We examined human pancreatic autopsy tissue from 66 lean, non-diabetic individuals aged from 30 to 102 years, grouped into deciles: 3rd (30–39 years), 4th (40–49 years), 5th (50–59 years), 6th (60–69 years), 7th (70–79 years), 8th (80–89 years) and 9th deciles (90+ years). Sections of pancreas were immunostained for glucagon and analyzed for fractional alpha-cell area. Population-based pancreatic volume data were used to calculate alpha-cell mass. Results With advanced age, the exocrine pancreas undergoes atrophy demonstrated by increased fat area (as % exocrine area) (0.05 ± 0.01 vs 1.6 ± 0.7% fat area of total exocrine pancreas, 3rd vs 9th decile, P < 0.05). Consequently, islet density increases with age (2.7 ± 0.4 vs 10.5 ± 3.3 islets/mm2, 3rd vs 9th decile, P < 0.05). Alpha-cell fractional area increases with advanced age (0.34 ± 0.05% vs 0.73 ± 0.26%, 3rd vs 9th decile, P < 0.05). However, alpha-cell mass remains constant at ~190 mg throughout the adult lifespan in lean, non-diabetic humans. Within islets, alpha-cell distribution between mantle and core is unchanged across deciles (1862 ± 220 vs 1945 ± 200 vs 1948 ± 139 alpha cells in islet mantle/mm2, 3rd vs 6th vs 9th decile, P = 0.93 and 1912 ± 442 vs 1449 ± 123 vs 1514 ± 168 alpha cells in islet core/mm2, 3rd vs 6th vs 9th decile, P = 0.47), suggesting that human islets retain their structural organization in the setting of age-related exocrine atrophy. Conclusions Consistent with our previous findings for beta-cell mass, alpha-cell mass remains constant in humans, even with advanced age. Pancreatic endocrine cells are much more robustly preserved than exocrine cells in aged humans, and islets maintain their structural integrity throughout life.

scholarly journals Delta Cell Hyperplasia in Adult Goto-Kakizaki (GK/MolTac) Diabetic Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-16 ◽  
Author(s):  
Lukáš Alán ◽  
Tomáš Olejár ◽  
Monika Cahová ◽  
Jaroslav Zelenka ◽  
Zuzana Berková ◽  
...  
Keyword(s):  
Beta Cell ◽  
Wistar Rats ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Cell Physiology ◽  
Gk Rat ◽  
Cell Hyperplasia ◽  
Gk Rats ◽  
Delta Cell ◽  
Delta Cells

Reduced beta cell mass in pancreatic islets (PI) of Goto-Kakizaki (GK) rats is frequently observed in this diabetic model, but knowledge on delta cells is scarce. Aiming to compare delta cell physiology/pathology of GK to Wistar rats, we found that delta cell number increased over time as did somatostatin mRNA and delta cells distribution in PI is different in GK rats. Subtle changes in 6-week-old GK rats were found. With maturation and aging of GK rats, disturbed cytoarchitecture occurred with irregular beta cells accompanied by delta cell hyperplasia and loss of pancreatic polypeptide (PPY) positivity. Unlike the constant glucose-stimulation index for insulin PI release in Wistar rats, this index declined with GK age, whereas for somatostatin it increased with age. A decrease of GK rat PPY serum levels was found. GK rat body weight decreased with increasing hyperglycemia. Somatostatin analog octreotide completely blocked insulin secretion, impaired proliferation at low autocrine insulin, and decreased PPY secretion and mitochondrial DNA in INS-1E cells. In conclusion, in GK rats PI, significant local delta cell hyperplasia and suspected paracrine effect of somatostatin diminish beta cell viability and contribute to the deterioration of beta cell mass. Altered PPY-secreting cells distribution amends another component of GK PI’s pathophysiology.

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