Effects of amylin on glucose metabolism and glycogenolysis in vivo and in vitro.

1990 ◽  
Vol 259 (3) ◽  
pp. E457 ◽  
Author(s):  
D A Young ◽  
R O Deems ◽  
R W Deacon ◽  
R H McIntosh ◽  
J E Foley
Keyword(s):  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Glucose Turnover ◽  
Metabolic Clearance ◽  
Tissue Samples ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Glucose Phosphorylation

The effects of amylin on glucose metabolism and glycogenolysis were examined in vivo and in vitro. Eighteen-hour-fasted rats were infused with 5 nmol.kg-1.min-1 amylin and [3-3H]glucose for 120 min. Blood glucose levels increased an average of 45% during the infusion. Glucose turnover measurements indicated that the overall rate of glucose appearance (Ra) did not change, but the metabolic clearance rate of glucose was decreased by 42%. Samples of liver, gastrocnemius, and soleus muscles were freeze-clamped at the end of the infusion period and analyzed for glycogen and glucose 6-phosphate levels. Glycogen levels were decreased in all tissue samples, whereas glucose 6-phosphate was elevated in gastrocnemius and soleus muscles. Isolated soleus muscles were incubated in vitro with 200 microU/ml of insulin and 1, 10, or 100 nM amylin. Amylin treatment had no effect on 3-O-methyl-D-glucose transport; however, 2-deoxy-D-glucose uptake was inhibited by 33 or 48% at 10 or 100 nM amylin, respectively. Glycogen levels were also decreased after treatment with 10 and 100 nM amylin. Glucose 6-phosphate levels were not affected by amylin treatment in the presence of insulin but were increased nearly twofold in its absence. The data suggest that amylin stimulates glycogenolysis and inhibits glucose uptake both in vivo and in vitro and that the inhibition of glucose uptake is due to inhibition of glucose phosphorylation (i.e., hexokinase).

Relationship of substrate level to turnover rate in fasted adult and newborn dogs

1988 ◽  
Vol 254 (2) ◽  
pp. E137-E143 ◽  
Author(s):  
S. Hulman ◽  
R. Kliegman ◽  
J. Heng ◽  
E. Crouser
Keyword(s):  
Blood Glucose ◽  
Glucose Metabolism ◽  
Inverse Function ◽  
Glucose Disposal ◽  
Glucose Turnover ◽  
Metabolic Clearance ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Glucose Clearance ◽  
Plasma Insulin Levels

Glucose turnover, clearance and response to insulin were determined in fasted newborn and adult dogs. Fasting levels of glucose and insulin and rates of glucose turnover and clearance were not different between the two groups. Blood glucose correlated with basal glucose turnover in newborn pups but not in adult dogs. Glucose turnover was not related to fasting plasma insulin levels. Glucose clearance was an inverse function of blood glucose levels among newborn but not adult dogs. Glucose clearance and blood glucose levels were not related to insulin concentrations. In response to euglycemic hyperinsulinemia, glucose metabolism increased 4-fold among adults but only 1.7-fold in pups. Hyperglycemic hyperinsulinemia increased glucose metabolism in both groups but to a much greater extent in the pups. Euglycemic hyperinsulinemia increased the metabolic clearance rate of glucose 4.2-fold among adults but only 1.8-fold in newborn dogs. In response to hyperglycemic hyperinsulinemia glucose clearance rates were now similar. Despite euglycemic hyperinsulinemia, the newborn dog had an attenuated response to insulin, demonstrating lower rates of glucose metabolism and glucose clearance. The response to the hyperglycemic stimuli suggests that maximal glucose uptake was not achieved during hyperinsulinemia alone. This response supports the concept of glucose-mediated regulation of glucose disposal in newborn animals.

In vitro analysis of glucose metabolism and embryonic growth in postimplantation rat embryos

Development ◽  
1987 ◽  
Vol 100 (3) ◽  
pp. 431-439 ◽  
Author(s):  
S.K. Ellington
Keyword(s):  
Glucose Metabolism ◽  
Embryonic Development ◽  
Glucose Uptake ◽  
Glucose Concentration ◽  
Culture Media ◽  
Rat Embryos ◽  
Embryonic Growth ◽  
Stage Of Development

The glucose metabolism and embryonic development of rat embryos during organogenesis was studied using embryo culture. Glucose uptake and embryonic growth and differentiation of 10.5-day explants (embryos + membranes) were limited by the decreasing glucose concentration, but not the increasing concentration of metabolites, in the culture media during the second 24 h of a 48 h culture. No such limitations were found on the embryonic development of 9.5-day explants during a 48 h culture although glucose uptake was slightly reduced at very low concentrations of glucose. From the head-fold stage to the 25-somite stage of development, glucose uptake was characteristic of the stage of development of the embryo and not the time it had been in culture. Embryonic growth of 9.5-day explants was similar to that previously observed in vivo. Glucose uptake by 9.5-day explants was dependent on the surface area of the yolk sac and was independent of the glucose concentration in the culture media (within the range of 9.4 to 2.5 mM). The proportion of glucose converted to lactate was 100% during the first 42h of culture then fell to about 50% during the final 6h. The protein contents of both the extraembryonic membranes and the embryo were dependent on the glucose uptake.

scholarly journals Oral DhHP-6 for the Treatment of Type 2 Diabetes Mellitus

2019 ◽  
Vol 20 (6) ◽  
pp. 1517 ◽  
Author(s):  
Kai Wang ◽  
Yu Su ◽  
Yuting Liang ◽  
Yanhui Song ◽  
Liping Wang
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Blood Glucose ◽  
Enzymatic Activity ◽  
Glucose Levels ◽  
Blood Glucose Levels

Type 2 diabetes mellitus (T2DM) is associated with pancreatic β-cell dysfunction which can be induced by oxidative stress. Deuterohemin-βAla-His-Thr-Val-Glu-Lys (DhHP-6) is a microperoxidase mimetic that can scavenge reactive oxygen species (ROS) in vivo. In our previous studies, we demonstrated an increased stability of linear peptides upon their covalent attachment to porphyrins. In this study, we assessed the utility of DhHP-6 as an oral anti-diabetic drug in vitro and in vivo. DhHP-6 showed high resistance to proteolytic degradation in vitro and in vivo. The degraded DhHP-6 product in gastrointestinal (GI) fluid retained the enzymatic activity of DhHP-6, but displayed a higher permeability coefficient. DhHP-6 protected against the cell damage induced by H2O2 and promoted insulin secretion in INS-1 cells. In the T2DM model, DhHP-6 reduced blood glucose levels and facilitated the recovery of blood lipid disorders. DhHP-6 also mitigated both insulin resistance and glucose tolerance. Most importantly, DhHP-6 promoted the recovery of damaged pancreas islets. These findings suggest that DhHP-6 in physiological environments has high stability against enzymatic degradation and maintains enzymatic activity. As DhHP-6 lowered the fasting blood glucose levels of T2DM mice, it thus represents a promising candidate for oral administration and clinical therapy.

scholarly journals Glycemic Variability in Diabetes Increases the Severity of Influenza

mBio ◽  
2020 ◽  
Vol 11 (2) ◽  
Author(s):  
Rebecca J. Marshall ◽  
Pornthida Armart ◽  
Katina D. Hulme ◽  
Keng Yih Chew ◽  
Alexandra C. Brown ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Glycemic Variability ◽  
Endothelial Barrier ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Severe Influenza ◽  
Increased Risk ◽  
History Of

ABSTRACT People with diabetes are two times more likely to die from influenza than people with no underlying medical condition. The mechanisms underlying this susceptibility are poorly understood. In healthy individuals, small and short-lived postprandial peaks in blood glucose levels occur. In diabetes mellitus, these fluctuations become greater and more frequent. This glycemic variability is associated with oxidative stress and hyperinflammation. However, the contribution of glycemic variability to the pathogenesis of influenza A virus (IAV) has not been explored. Here, we used an in vitro model of the pulmonary epithelial-endothelial barrier and novel murine models to investigate the role of glycemic variability in influenza severity. In vitro, a history of glycemic variability significantly increased influenza-driven cell death and destruction of the epithelial-endothelial barrier. In vivo, influenza virus-infected mice with a history of glycemic variability lost significantly more body weight than mice with constant blood glucose levels. This increased disease severity was associated with markers of oxidative stress and hyperinflammation both in vitro and in vivo. Together, these results provide the first indication that glycemic variability may help drive the increased risk of severe influenza in people with diabetes mellitus. IMPORTANCE Every winter, people with diabetes are at increased risk of severe influenza. At present, the mechanisms that cause this increased susceptibility are unclear. Here, we show that the fluctuations in blood glucose levels common in people with diabetes are associated with severe influenza. These data suggest that glycemic stability could become a greater clinical priority for patients with diabetes during outbreaks of influenza.

Impact of in vivo fatty acid oxidation blockade on glucose turnover and muscle glucose metabolism during low-dose AICAR infusion

2006 ◽  
Vol 291 (5) ◽  
pp. E1131-E1140 ◽  
Author(s):  
Michael Christopher ◽  
Christian Rantzau ◽  
Zhi-Ping Chen ◽  
Rodney Snow ◽  
Bruce Kemp ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Glucose Metabolism ◽  
Fatty Acid Oxidation ◽  
Low Dose ◽  
Whole Body ◽  
Glucose Turnover ◽  
Acid Oxidation ◽  
Metabolic Clearance ◽  
The Impact

AMPK plays a central role in influencing fuel usage and selection. The aim of this study was to analyze the impact of low-dose AMP analog 5-aminoimidazole-4-carboxamide-1-β-d-ribosyl monophosphate (ZMP) on whole body glucose turnover and skeletal muscle (SkM) glucose metabolism. Dogs were restudied after prior 48-h fatty acid oxidation (FAOX) blockade by methylpalmoxirate (MP; 5 × 12 hourly 10 mg/kg doses). During the basal equilibrium period (0–150 min), fasting dogs ( n = 8) were infused with [3-3H]glucose followed by either 2-h saline or AICAR (1.5–2.0 mg·kg−1·min−1) infusions. SkM was biopsied at completion of each study. On a separate day, the same protocol was undertaken after 48-h in vivo FAOX blockade. The AICAR and AICAR + MP studies were repeated in three chronic alloxan-diabetic dogs. AICAR produced a transient fall in plasma glucose and increase in insulin and a small decline in free fatty acid (FFA). Parallel increases in hepatic glucose production (HGP), glucose disappearance (Rd tissue), and glycolytic flux (GF) occurred, whereas metabolic clearance rate of glucose (MCRg) did not change significantly. Intracellular SkM glucose, glucose 6-phosphate, and glycogen were unchanged. Acetyl-CoA carboxylase (ACC∼pSer221) increased by 50%. In the AICAR + MP studies, the metabolic responses were modified: the glucose was lower over 120 min, only minor changes occurred with insulin and FFA, and HGP and Rd tissue responses were markedly attenuated, but MCRg and GF increased significantly. SkM substrates were unchanged, but ACC∼pSer221 rose by 80%. Thus low-dose AICAR leads to increases in HGP and SkM glucose uptake, which are modified by prior FAox blockade.

scholarly journals Lactate: A Preferred Fuel for Human Brain Metabolism in Vivo

2003 ◽  
Vol 23 (6) ◽  
pp. 658-664 ◽  
Author(s):  
Diarmuid Smith ◽  
Andrew Pernet ◽  
William A. Hallett ◽  
Emma Bingham ◽  
Paul K. Marsden ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Human Subjects ◽  
Random Order ◽  
Glucose Levels ◽  
Positron Emission ◽  
Fdg Pet Scan ◽  
Global Brain ◽  
Lactate Infusion

Recent in vitro studies suggest that lactate, rather than glucose, may be the preferred fuel for neuronal metabolism. The authors examined the effect of lactate on global brain glucose uptake in euglycemic human subjects using 18fluorodeoxyglucose (FDG) positron emission tomography (PET). Eight healthy men, aged 40 to 54 years, underwent a 60-minute FDG-PET scan on two occasions in random order. On one occasion, 6.72% sodium lactate was infused at a rate of 50 μmol · kg−1 · min−1 for 20 minutes and then reduced to 30 μmol · kg−1 · min−1; 1.4% sodium bicarbonate was infused as a control on the other occasion. Plasma glucose levels were not different between the two groups (5.3 ± 0.23 and 5.3 ± 0.24 mmol/L, P = 0.55). Plasma lactate was significantly elevated by lactate infusion (4.08 ± 0.35 vs. 0.63 ± 0.22 mmol/L, P < 0.0005. The whole-brain rate of glucose uptake was significantly reduced by approximately 17% during lactate infusion (0.195 ± 0.022 vs. 0.234 ± 0.020 μmol · g−1 · min−1, P = 0.001). The authors conclude that, in vivo in humans, circulating lactate is used by the brain at euglycemia, with sparing of glucose.

scholarly journals Zinc Regulates Glucose Metabolism of the Spinal Cord and Neurons and Promotes Functional Recovery after Spinal Cord Injury through the AMPK Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-27
Author(s):  
Hengshuo Hu ◽  
Nan Xia ◽  
Jiaquan Lin ◽  
Daoyong Li ◽  
Chuanjie Zhang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Nervous System ◽  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Functional Recovery ◽  
Glucose Metabolism Disorders ◽  
Cord Injury

Spinal cord injury (SCI) is a traumatic disease that can cause severe nervous system dysfunction. SCI often causes spinal cord mitochondrial dysfunction and produces glucose metabolism disorders, which affect neuronal survival. Zinc is an essential trace element in the human body and plays multiple roles in the nervous system. This experiment is intended to evaluate whether zinc can regulate the spinal cord and neuronal glucose metabolism and promote motor functional recovery after SCI. Then we explore its molecular mechanism. We evaluated the function of zinc from the aspects of glucose uptake and the protection of the mitochondria in vivo and in vitro. The results showed that zinc elevated the expression level of GLUT4 and promoted glucose uptake. Zinc enhanced the expression of proteins such as PGC-1α and NRF2, reduced oxidative stress, and promoted mitochondrial production. In addition, zinc decreased neuronal apoptosis and promoted the recovery of motor function in SCI mice. After administration of AMPK inhibitor, the therapeutic effect of zinc was reversed. Therefore, we concluded that zinc regulated the glucose metabolism of the spinal cord and neurons and promoted functional recovery after SCI through the AMPK pathway, which is expected to become a potential treatment strategy for SCI.

scholarly journals ANTI-DIABETIC EFFECTS OF GLUCOMANNO-OLIGOSACCHARIDES VIA AMPK ACTIVATION IN C2C12 MYOTUBES

2021 ◽  
Vol 59 (4) ◽  
pp. 467
Author(s):  
Thien Truong Do ◽  
Nu Thi Tran ◽  
Que Nguyet Thi Do ◽  
Nhi Thi Y Tran
Keyword(s):  
C2c12 Myotubes ◽  
Control Group ◽  
Ampk Activation ◽  
Independent Manner ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Ampk Phosphorylation ◽  
Amp Activated Protein Kinase

Abstract-HCTN7. In this paper, antidiabetic activities of glucomanno-oligosaccharides (GMO) in vitro and in vivo were investigated. GMO significantly increased AMP-activated protein kinase (AMPK) phosphorylation in a concentration-independent manner. Treatment with 100μg/ml and 50μg/ml of GMO for 1 hour caused 1.47-fold and 1.81-fold phosphorylation of AMPK, respectively. Oral administration of GMO (6g/kg-1 of body weight day-1) lowered blood glucose levels (p < 0.05) at 120 min as compared to control group. These results suggested that GMO exhibited anti-diabetic effects via activation of AMPK and could be useful for diabetes prevention

scholarly journals “Oil-soluble” Reversed Lipid Nanoparticles for Oral Insulin Delivery

2020 ◽  
Author(s):  
Tao Wang ◽  
Dongqin Quan
Keyword(s):  
Oral Absorption ◽  
Insulin Delivery ◽  
Lipid Nanoparticles ◽  
Oral Insulin ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Transmission Electron ◽  
Insulin Solution

Abstract Background In this study, we aimed to design a novel oral insulin delivery system, named “oil-soluble” reversed lipid nanoparticles (ORLN), in which a hydrophilic insulin molecule is encapsulated by a phospholipid (PC) shell and dissolved in oil to prevent the enzymatic degradation of insulin. ORLN was characterized by transmission electron microscopy and dynamic light scattering. Results In vitro enzymatic stability studies showed higher concentrations of insulin in cells incubated with ORLN-encapsulated insulin than in those incubated with free insulin solution in artificial intestinal fluid (pH 6.5). The protective effect of ORLN was attributed to its special release behavior and the formulation of the PC shell and oil barrier. Furthermore, an in vivo oral efficacy study confirmed that blood glucose levels were markedly decreased after ORLN administration in both healthy and diabetic mice. In vivo pharmacokinetic results showed that the bioavailability of ORLN-conjugated insulin was approximately 28.7% relative to that of the group subcutaneously administered with an aqueous solution of insulin, indicating enhanced oral absorption. Conclusions In summary, the ORLN system developed here shows promise as a nanocarrier for improving the oral absorption of insulin.

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