Hyperinsulinemic-euglycemic Clamps in Conscious, Unrestrained Mice

Ayala, Julio E.; Bracy, Deanna P.; Malabanan, Carlo M.; James, Freyja D.; Ansari, Tasneem; Fueger, Patrick T.; McGuinness, Owen P.; Wasserman, David H.

doi:10.3791/3188-v

Cited by 23 publications

(16 citation statements)

References 15 publications

(18 reference statements)

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“…Hyperinsulinemic-euglycemic clamp. Mice were anesthetized under 2% (v/v) isoflurane and the left common carotid artery and the right jugular vein were catheterized for sampling and infusions, respectively, as previously described (51). On the day of the experiment, food was removed at 8 am.…”

Section: Methodsmentioning

confidence: 99%

Cyclooxygenase-2 in adipose tissue macrophages limits adipose tissue dysfunction in obese mice

Pan¹,

Cao²,

Tang³

et al. 2022

Journal of Clinical Investigation

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Section: Methodsmentioning

confidence: 99%

Cyclooxygenase-2 in adipose tissue macrophages limits adipose tissue dysfunction in obese mice

Pan¹,

Cao²,

Tang³

et al. 2022

Journal of Clinical Investigation

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“…Plasma glucose concentrations were measured using a glucose analyser (Analox). These values were used for the calculation of R d and R a as described (Ayala et al, 2011;Ayala et al, 2006;Ayala et al, 2010;McGuinness et al, 2019). R d and R a rates were calculated using Steele's equations (Steele et al, 1956).…”

Section: Methods Detailsmentioning

confidence: 99%

Exposure to Static Magnetic and Electric Fields Treats Type 2 Diabetes

Carter¹,

Huang²,

Searby³

et al. 2022

Cell Metabolism

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“…Hyperglycemic clamps were used to quantify insulin secretion in vivo . Surgical procedures have been described in detail previously [32, 33]. Briefly, mice were anesthetized with isoflurane, and the carotid artery and jugular vein were catheterized.…”

Section: Methodsmentioning

confidence: 99%

Pancreatic Deletion of Mitogen-inducible Gene 6 Promotes Beta Cell Proliferation Following Destruction

Bauer

Chen

et al. 2023

Preprint

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Type 1 Diabetes (T1D) is caused by autoimmune-mediated beta cell destruction. Following beta cell injury, the pancreas attempts to launch a cellular repair and regenerative program, yet it fails to completely restore functional beta cell mass. One component of this regenerative program is epidermal growth factor receptor (EGFR) signaling. However, upon irreparable beta cell damage, EGFR signaling is dampened, disrupting attempts to restore functional beta cell mass and maintain normoglycemia. We previously demonstrated that the negative feedback inhibitor of EGFR, Mitogen-inducible gene 6 (Mig6), is induced by the pro-inflammatory cytokines central to the autoimmune-mediated beta cell destruction. We also established that pro-inflammatory cytokines suppress EGFR activation, and siRNA-mediated suppression of Mig6 restores EGFR signaling. Thus, we hypothesized that pro-inflammatory cytokines induce nitric oxide production and that in turn induced Mig6, disrupting EGFR repair mechanisms. We determined that NO induces Mig6, attenuating EGFR signaling, and NO synthase inhibition blocks the cytokine-mediated induction of Mig6, thereby restoring cytokine-impaired EGFR signaling. To that end, we treated mice lacking pancreatic Mig6 and control mice with a streptozotocin (STZ) to induce beta cell death and diabetes in a way that mimics the onset and progression of T1D. Whereas STZ-treated control mice became hyperglycemic and had reduced beta cell mass, STZ-treated Mig6 pancreas-specific knock out (PKO) mice remained euglycemic and glucose tolerant due to preserved beta cell mass. The restoration of beta cell mass in PKO mice was accompanied by enhanced beta cell proliferation. Thus, our work suggests that Mig6 is a promising target to preserve beta cell mass before overt T1D.

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Hyperinsulinemic-euglycemic Clamps in Conscious, Unrestrained Mice

Cited by 23 publications

References 15 publications

Cyclooxygenase-2 in adipose tissue macrophages limits adipose tissue dysfunction in obese mice

Cyclooxygenase-2 in adipose tissue macrophages limits adipose tissue dysfunction in obese mice

Exposure to Static Magnetic and Electric Fields Treats Type 2 Diabetes

Pancreatic Deletion of Mitogen-inducible Gene 6 Promotes Beta Cell Proliferation Following Destruction

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