Training Pigs for Oral Glucose Tolerance Test—Six Years’ Experience of a Refined Model

Manell, Elin; Hedenqvist, Patricia; Jensen-Waern, Marianne

doi:10.3390/ani11061677

Cited by 4 publications

(4 citation statements)

References 2 publications

(9 reference statements)

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“…A total of 384 references were identified by electronic search; 338 full-text studies were evaluated in accordance with the eligibility criteria and 290 were excluded. Finally, 48 studies [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 ] complied with all the established eligibility criteria and were included in the study ( Figure 1 ).…”

Section: Resultsmentioning

confidence: 99%

Refinement in the European Union: A Systematic Review

Díez-Solinska

Vegas

Azkona

2022

Animals

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Refining experiments and housing conditions so as to cause the minimum possible pain and distress is one of the three principles (3Rs) on which Directive 2010/63/EU is based. In this systematic review, we aimed to identify and summarize published advances in the refinement protocols made by European Union-based research groups from 2011 to 2021, and to determine whether or not said research was supported by European or national grants. We included 48 articles, the majority of which were related to improvements in experimental procedures (37/77.1%) for mice (26/54.2%) and were written by research groups belonging to universities (36/57.1%) and from the United Kingdom (21/33.9%). More than two thirds (35/72.9%) of the studies received financial support, 26 (mostly British) at a national level and 8 at a European level. Our results indicated a clear willingness among the scientific community to improve the welfare of laboratory animals, as although funding was not always available or was not specifically granted for this purpose, studies were published nonetheless. However, in addition to institutional support based on legislation, more financial support is needed. We believe that more progress would have been made in refinement during these years if there had been more specific financial support available at both the national and European Union levels since our data suggest that countries investing in refinement have the greatest productivity in successfully publishing refinements.

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Section: Resultsmentioning

confidence: 99%

Refinement in the European Union: A Systematic Review

Díez-Solinska

Vegas

Azkona

2022

Animals

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“…The oral glucose tolerance tests (OGTTs) consisted of oral consumption of 75 g of glucose dissolved in 100 mL of diet Gatorade. Oral glucose tolerance tests are widely used to measure glycemic control ( Khan et al, 2019 ; Kuo et al, 2021 ) including in swine ( Manell et al, 2016 , 2021 ). An IV port was placed in the jugular vein.…”

Section: Methodsmentioning

confidence: 99%

Use of a bio-electronic device comprising of targeted dual neuromodulation of the hepatic and celiac vagal branches demonstrated enhanced glycemic control in a type 2 diabetic rat model as well as in an Alloxan treated swine model

Waataja

Nihalani²,

Honda³

et al. 2022

Front. Neurosci.

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BackgroundThere is an unmet need for new type 2 diabetes treatments providing improved efficacy, durability and customized to improve patient’s compliance. Bio-electronic neuromodulation of Vagus nerve branches innervating organs that regulate plasma glucose, may be a method for treating type 2 diabetes. The pancreas has been shown to release insulin during Vagus stimulation. The hepatic vagal branch, innervating the liver, has been shown to decrease glucose release and decrease insulin resistance following ligation. However, standalone stimulation of the Vagus nerve has shown mixed results and Vagus nerve ligation has undesirable effects. Little is known; however, of the effect on plasma glucose with combined neuromodulation consisting of stimulation of the celiac branch innervating the pancreas with simultaneous high frequency alternating current (HFAC) blockade of the hepatic branch. This study tested the effects of this approach on increasing glycemic control in rat a model of type 2 diabetes and Alloxan treated swine.Materials and methodsZucker obese (fatty) male rats (ZDF fa/fa) were used as a model of type 2 diabetes as well as glucose intolerant Alloxan treated swine. In ZDF rat experiments glycemic control was accessed with an intravenous glucose tolerance test during HFAC-induced hepatic branch block with concurrent celiac stimulation (HFAC + stimulation). In swine experiments glycemic control was accessed by an oral glucose tolerance test during HFAC + stimulation. Insulin measurements were taken prior to and following swine experiments giving insight into beta cell exhaustion. Histopathology was conducted to determine safety of HFAC + stimulation on Vagal branches.ResultsZucker rats demonstrated a significant improvement to an intravenous glucose tolerance test during HFAC + stimulation compared to sham. There was no significant difference from sham compared to hepatic vagotomy or celiac stimulation. In Alloxan treated swine, when subjected to HFAC + stimulation, there was a significant improvement in glycemic control as measured by an improvement on oral glucose tolerance tests and a decrease in fasting plasma glucose. Insulin responses were similar prior to and following HFAC + stimulation experiments. Histopathology demonstrated healthy swine Vagus nerves.ConclusionElectrical blockade of the hepatic Vagus branch with simultaneous stimulation of the celiac Vagus branch may be a novel, adjustable and localized approach for a treatment of type 2 diabetes.

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“…Two Viking neuroregulators (ReShape ences Inc., Irvine, CA, USA) and four Viking Model 2200-47E leads (ReShape Life Swine were trained to wear a jacket to house mobile charging units for future charging sessions and to drink 100 mL of diet Gatorade delivered through a syringe. Oral consumption of 75 g of glucose dissolved in 100 mL of diet Gatorade was administered at the start of the OGTTs, which are widely used to assess glycemic control in swine [66,67].…”

Section: Hfac + Stimulation Experimentsmentioning

confidence: 99%

Combining Celiac and Hepatic Vagus Nerve Neuromodulation Reverses Glucose Intolerance and Improves Glycemic Control in Pre- and Overt-Type 2 Diabetes Mellitus

Waataja,

Asp,

Billington

2023

Biomedicines

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Neurological disorders and type 2 diabetes mellitus (T2DM) are deeply intertwined. For example, autonomic neuropathy contributes to the development of T2DM and continued unmanaged T2DM causes further progression of nerve damage. Increasing glycemic control has been shown to prevent the onset and progression of diabetic autonomic neuropathies. Neuromodulation consisting of combined stimulation of celiac vagal fibers innervating the pancreas with concurrent electrical blockade of neuronal hepatic vagal fibers innervating the liver has been shown to increase glycemic control in animal models of T2DM. The present study demonstrated that the neuromodulation reversed glucose intolerance in alloxan-treated swine in both pre- and overt stages of T2DM. This was demonstrated by improved performance on oral glucose tolerance tests (OGTTs), as assessed by area under the curve (AUC). In prediabetic swine (fasting plasma glucose (FPG) range: 101–119 mg/dL) the median AUC decreased from 31.9 AUs (IQR = 28.6, 35.5) to 15.9 AUs (IQR = 15.1, 18.3) p = 0.004. In diabetic swine (FPG range: 133–207 mg/dL) the median AUC decreased from 54.2 AUs (IQR = 41.5, 56.6) to 16.0 AUs (IQR = 15.4, 21.5) p = 0.003. This neuromodulation technique may offer a new treatment for T2DM and reverse glycemic dysregulation at multiple states of T2DM involved in diabetic neuropathy including at its development and during progression.

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Training Pigs for Oral Glucose Tolerance Test—Six Years’ Experience of a Refined Model

Cited by 4 publications

References 2 publications

Refinement in the European Union: A Systematic Review

Refinement in the European Union: A Systematic Review

Use of a bio-electronic device comprising of targeted dual neuromodulation of the hepatic and celiac vagal branches demonstrated enhanced glycemic control in a type 2 diabetic rat model as well as in an Alloxan treated swine model

Combining Celiac and Hepatic Vagus Nerve Neuromodulation Reverses Glucose Intolerance and Improves Glycemic Control in Pre- and Overt-Type 2 Diabetes Mellitus

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