Regulation of glucose transporters and hexose uptake in 3T3-L1 adipocytes: glucagon-like peptide-1 and insulin interactions

1997 ◽  
Vol 19 (3) ◽  
pp. 241-248 ◽  
Author(s):  
Y Wang ◽  
HK Kole ◽  
C Montrose-Rafizadeh ◽  
R Perfetti ◽  
M Bernier ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Glucose Transporter ◽  
Prolonged Exposure ◽  
Lipid Synthesis ◽  
Glucose Transporters ◽  
Fed State ◽  
Protein Levels ◽  
Gut Hormone ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Glucagon-like peptide-1 (7-36 amide) (GLP-1) is known to increase insulin release when given as a bolus in the fasted and fed state. GLP-1 also increases glucose uptake and lipid synthesis in cultured adipocytes. In this study we investigated the effects of GLP-1 on glucose uptake and on the levels of expression of the facilitative glucose transporters, GLUT1 and GLUT4, in fully differentiated 3T3-L1 adipocytes. Cells were incubated with GLP-1 (10 nM) with or without insulin (10 and 100 nM) for 24 h. Under these conditions, GLP-1 alone caused an increase in basal and acute insulin-stimulated glucose uptake along with an increase in GLUT1 and GLUT4 protein levels. However, there was no change in the expression of GLUT1 and GLUT4 mRNAs. In the absence of GLP-1, prolonged exposure to insulin caused a marked reduction in the levels of GLUT4 mRNA and protein, and an inhibition of glucose uptake after an acute exposure to insulin. This insulin-induced down-regulation of GLUT4 was prevented when GLP-1 was present during the 24-h treatment. In contrast, the acute insulin-stimulated glucose uptake could not be restored by GLP-1. GLP-1 is therefore the first gut hormone shown to be capable of modulating glucose transporter levels in cultured adipocytes.

scholarly journals [Gly²]-GLP-2, But Not Glucagon or [D-Ala²]-GLP-1, Controls Collagen Crosslinking in Murine Osteoblast Cultures

2021 ◽  
Vol 12 ◽  
Author(s):  
Aleksandra Mieczkowska ◽  
Beatrice Bouvard ◽  
Erick Legrand ◽  
Guillaume Mabilleau
Keyword(s):  
Gut Hormones ◽  
Receptor Expression ◽  
Post Processing ◽  
Collagen Crosslinking ◽  
Protein Levels ◽  
Gut Hormone ◽  
Fourier Transform Infrared Microspectroscopy ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Hormone Receptor Expression

Bone tissue is organized at the molecular level to resist fracture with the minimum of bone material. This implies that several modifications of the extracellular matrix, including enzymatic collagen crosslinking, take place. We previously highlighted the role of several gut hormones in enhancing collagen maturity and bone strength. The present study investigated the effect of proglucagon-derived peptides on osteoblast-mediated collagen post-processing. Briefly, MC3T3-E1 murine osteoblasts were cultured in the presence of glucagon (GCG), [D-Ala²]-glucagon-like peptide-1 ([D-Ala²]-GLP-1), and [Gly²]-glucagon-like peptide-2 ([Gly²]-GLP-2). Gut hormone receptor expression at the mRNA and protein levels were investigated by qPCR and Western blot. Extent of collagen postprocessing was examined by Fourier transform infrared microspectroscopy. GCG and GLP-1 receptors were not evidenced in osteoblast cells at the mRNA and protein levels. However, it is not clear whether the known GLP-2 receptor is expressed. Nevertheless, administration of [Gly²]-GLP-2, but not GCG or [D-Ala²]-GLP-1, led to a dose-dependent increase in collagen maturity and an acceleration of collagen post-processing. This mechanism was dependent on adenylyl cyclase activation. In conclusion, the present study highlighted a direct effect of [Gly²]-GLP-2 to enhance collagen post-processing and crosslinking maturation in murine osteoblast cultures. Whether this effect is translatable to human osteoblasts remains to be elucidated.

Subcutaneous glucagon-like peptide-1 (7-36) amide is insulinotropic and can cause hypoglycaemia in fasted healthy subjects

1998 ◽  
Vol 95 (6) ◽  
pp. 719-724 ◽  
Author(s):  
C. Mark B. EDWARDS ◽  
Jeannie F. TODD ◽  
Mohammad A. GHATEI ◽  
Stephen R. BLOOM
Keyword(s):  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Plasma Glucose ◽  
Healthy Subjects ◽  
Therapeutic Potential ◽  
Double Blind ◽  
Gut Hormone ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

1. Glucagon-like peptide-1 (7-36) amide (GLP-1) is a gut hormone released postprandially that stimulates insulin secretion, suppresses glucagon secretion and delays gastric emptying. The insulinotropic action of GLP-1 is more potent under hyperglycaemic conditions. Several published studies have indicated the therapeutic potential of subcutaneous GLP-1 in non-insulin-dependent (Type 2) diabetes mellitus. 2. We investigated whether subcutaneous GLP-1, at a dose shown to improve glycaemic control in early Type 2 diabetes, is insulinotropic at normal fasting glucose concentrations. A double-blind, randomized, crossover study of 10 healthy subjects injected with GLP-1 or saline subcutaneously after a 16 h fast was performed. The effect on cardiovascular parameters was also examined. 3. GLP-1 caused a near 5-fold rise in plasma insulin concentration. After treatment with GLP-1, circulating plasma glucose concentrations fell below the normal range in all subjects. One subject had symptoms of hypoglycaemia after GLP-1. A rise in pulse rate was found which correlated with the fall in plasma glucose concentration. An increase in blood pressure occurred with GLP-1 injection which was seen at the same time as the rise in plasma GLP-1 concentrations. 4. This study indicates that subcutaneous GLP-1 can override the normal homoeostatic mechanism maintaining fasting plasma glucose in man, and is also associated with an increase in blood pressure.

Effect of intraportal glucagon-like peptide-1 on glucose metabolism in conscious dogs

2003 ◽  
Vol 284 (5) ◽  
pp. E1027-E1036 ◽  
Author(s):  
Makoto Nishizawa ◽  
Mary Courtney Moore ◽  
Masakazu Shiota ◽  
Stephanie M. Gustavson ◽  
Wanda L. Snead ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Conscious Dogs ◽  
Glucose Disposal ◽  
Control Group ◽  
Hepatic Glucose ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Hepatic Glucose Uptake ◽  
Arteriovenous Difference ◽  
Intraportal Infusion

Arteriovenous difference and tracer ([3-3H]glucose) techniques were used in 42-h-fasted conscious dogs to identify any insulin-like effects of intraportally administered glucagon-like peptide 1-(7–36)amide (GLP-1). Each study consisted of an equilibration, a basal, and three 90-min test periods (P1, P2, and P3) during which somatostatin, intraportal insulin (3-fold basal) and glucagon (basal), and peripheral glucose were infused. Saline was infused intraportally in P1. During P2 and P3, GLP-1 was infused intraportally at 0.9 and 5.1 pmol · kg−1 · min−1in eight dogs, at 10 and 20 pmol · kg−1 · min−1in seven dogs, and at 0 pmol · kg−1 · min−1in eight dogs (control group). Net hepatic glucose uptake was significantly enhanced during GLP-1 infusion at 20 pmol · kg−1 · min−1[21.8 vs. 13.4 μmol · kg−1 · min−1(control), P < 0.05]. Glucose utilization was significantly increased during infusion at 10 and 20 pmol · kg−1 · min−1[87.3 ± 8.3 and 105.3 ± 12.8, respectively, vs. 62.2 ± 5.3 and 74.7 ± 7.4 μmol · kg−1 · min−1(control), P < 0.05]. The glucose infusion rate required to maintain hyperglycemia was increased ( P < 0.05) during infusion of GLP-1 at 5.1, 10, and 20 pmol · kg−1 · min−1(22, 36, and 32%, respectively, greater than control). Nonhepatic glucose uptake increased significantly during delivery of GLP-1 at 5.1 and 10 pmol · kg−1 · min−1(25 and 46% greater than control) and tended ( P = 0.1) to increase during GLP-1 infusion at 20 pmol · kg−1 · min−1(24% greater than control). Intraportal infusion of GLP-1 at high physiological and pharmacological rates increased glucose disposal primarily in nonhepatic tissues.

Functional Expression of Sodium-Dependent Glucose Transporter in Amelogenesis

2020 ◽  
Vol 99 (8) ◽  
pp. 977-986
Author(s):  
H. Ida-Yonemochi ◽  
K. Otsu ◽  
H. Harada ◽  
H. Ohshima
Keyword(s):  
Organ Culture ◽  
Glucose Uptake ◽  
Glucose Transport ◽  
Glucose Transporter ◽  
Glucose Transporters ◽  
Maturation Stage ◽  
Sodium Dependent ◽  
Tooth Morphogenesis

Glucose is an essential source of energy for mammalian cells and is transported into the cells by glucose transporters. There are 2 types of glucose transporters: one is a passive glucose transporter, GLUT ( SLC2A), and the other is a sodium-dependent active glucose transporter, SGLT ( SLC5A). We previously reported that the expression of GLUTs during tooth development is precisely and spatiotemporally controlled and that the glucose uptake mediated by GLUT1 plays a crucial role in early tooth morphogenesis and tooth size determination. This study aimed to clarify the localization and roles of SGLT1 and SGLT2 in murine ameloblast differentiation by using immunohistochemistry, immunoelectron microscopy, an in vitro tooth organ culture experiment, and in vivo administration of an inhibitor of SGLT1/2, phloridzin. SGLT1, which has high affinity with glucose, was immunolocalized in the early secretory ameloblasts and the ruffle-ended ameloblasts in the maturation stage. However, SGLT2, which has high glucose transport capacity, was observed in the stratum intermedium, papillary layer, and ameloblasts at the maturation stage and colocalized with Na+-K+-ATPase. The inhibition of SGLT1/2 by phloridzin in the tooth germs induced the disturbance of ameloblast differentiation and enamel matrix formation both in vitro (organ culture) and in vivo (mouse model). The expression of SGLT1 and SGLT2 was significantly upregulated in hypoxic conditions in the ameloblast-lineage cells. These findings suggest that the active glucose uptake mediated by SGLT1 and SGLT2 is strictly regulated and dependent on the intra- and extracellular microenvironments during tooth morphogenesis and that the appropriate passive and active glucose transport is an essential event in amelogenesis.

scholarly journals Cephalic phase secretion of insulin and other enteropancreatic hormones in humans

2016 ◽  
Vol 310 (1) ◽  
pp. G43-G51 ◽  
Author(s):  
Simon Veedfald ◽  
Astrid Plamboeck ◽  
Carolyn F. Deacon ◽  
Bolette Hartmann ◽  
Filip K. Knop ◽  
...  
Keyword(s):  
Hormone Secretion ◽  
Sham Feeding ◽  
C Peptide ◽  
Healthy Men ◽  
Glucose Levels ◽  
Gut Hormone ◽  
Cephalic Phase ◽  
Hormone Responses ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Enteropancreatic hormone secretion is thought to include a cephalic phase, but the evidence in humans is ambiguous. We studied vagally induced gut hormone responses with and without muscarinic blockade in 10 glucose-clamped healthy men (age: 24.5 ± 0.6 yr, means ± SE; body mass index: 24.0 ± 0.5 kg/m2; HbA1c: 5.1 ± 0.1%/31.4 ± 0.5 mmol/mol). Cephalic activation was elicited by modified sham feeding (MSF, aka “chew and spit”) with or without atropine (1 mg bolus 45 min before MSF + 80 ng·kg−1·min−1 for 2 h). To mimic incipient prandial glucose excursions, glucose levels were clamped at 6 mmol/l on all days. The meal stimulus for the MSF consisted of an appetizing breakfast. Participants (9/10) also had a 6 mmol/l glucose clamp without MSF. Pancreatic polypeptide (PP) levels rose from 6.3 ± 1.1 to 19.9 ± 6.8 pmol/l (means ± SE) in response to MSF and atropine lowered basal PP levels and abolished the MSF response. Neither insulin, C-peptide, glucose-dependent insulinotropic polypeptide (GIP), nor glucagon-like peptide-1 (GLP-1) levels changed in response to MSF or atropine. Glucagon and ghrelin levels were markedly attenuated by atropine prior to and during the clamp: at t = 105 min on the atropine (ATR) + clamp (CLA) + MSF compared with the saline (SAL) + CLA and SAL + CLA + MSF days; baseline-subtracted glucagon levels were −10.7 ± 1.1 vs. −4.0 ± 1.1 and −4.7 ± 1.9 pmol/l (means ± SE), P < 0.0001, respectively; corresponding baseline-subtracted ghrelin levels were 303 ± 36 vs. 39 ± 38 and 3.7 ± 21 pg/ml (means ± SE), P < 0.0001. Glucagon and ghrelin levels were unaffected by MSF. Despite adequate PP responses, a cephalic phase response was absent for insulin, glucagon, GLP-1, GIP, and ghrelin.

Effects of intraduodenal fatty acids on appetite, antropyloroduodenal motility, and plasma CCK and GLP-1 in humans vary with their chain length

2004 ◽  
Vol 287 (3) ◽  
pp. R524-R533 ◽  
Author(s):  
Kate L. Feltrin ◽  
Tanya J. Little ◽  
James H. Meyer ◽  
Michael Horowitz ◽  
Andre J. P. M. Smout ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Chain Length ◽  
Energy Intake ◽  
Decanoic Acid ◽  
Double Blind ◽  
Intraduodenal Infusion ◽  
Gut Hormone ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Intraduodenal Administration

The gastrointestinal effects of intraluminal fats may be critically dependent on the chain length of fatty acids released during lipolysis. We postulated that intraduodenal administration of lauric acid (12 carbon atoms; C12) would suppress appetite, modulate antropyloroduodenal pressure waves (PWs), and stimulate the release of cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1) more than an identical dose of decanoic acid (10 carbon atoms; C10). Eight healthy males (19–47 yr old) were studied on three occasions in a double-blind, randomized fashion. Appetite perceptions, antropyloroduodenal PWs, and plasma CCK and GLP-1 concentrations were measured during a 90-min intraduodenal infusion of 1) C12, 2) C10, or 3) control (rate: 2 ml/min, 0.375 kcal/min for C12/C10). Energy intake at a buffet meal, immediately after completion of the infusion, was also quantified. C12, but not C10, suppressed appetite perceptions ( P < 0.001) and energy intake (control: 4,604 ± 464 kJ, C10: 4,109 ± 588 kJ, and C12: 1,747 ± 632 kJ; P < 0.001, C12 vs. control/C10). C12, but not C10, also induced nausea ( P < 0.001). C12 stimulated basal pyloric pressures and isolated pyloric PWs and suppressed antral and duodenal PWs compared with control ( P < 0.05 for all). C10 transiently stimulated isolated pyloric PWs ( P = 0.001) and had no effect on antral PWs but markedly stimulated duodenal PWs ( P = 0.004). C12 and C10 increased plasma CCK ( P < 0.001), but the effect of C12 was substantially greater ( P = 0.001); C12 stimulated GLP-1 ( P < 0.05), whereas C10 did not. In conclusion, there are major differences in the effects of intraduodenal C12 and C10, administered at 0.375 kcal/min, on appetite, energy intake, antropyloroduodenal PWs, and gut hormone release in humans.

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