Individual Mice Can Be Distinguished by the Period of Their Islet Calcium Oscillations

Nunemaker, Craig S.; Zhang, Min; Wasserman, David H.; McGuinness, Owen P.; Powers, Alvin C.; Bertram, Richard; Sherman, Arthur; Satin, Leslie S.

doi:10.2337/diabetes.54.12.3517

Cited by 88 publications

(98 citation statements)

References 52 publications

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“…For example, hyperglycemic clamps, in which glucose is infused at a variable rate to maintain hyperglycemia relative to fasting glucose, can be used to assess endogenous pancreatic function in vivo 2,20,21 . The measurement of first phase insulin secretion during this test requires frequent acquisition of blood samples (i.e every 2-5 min), which is not feasible when obtaining samples from the tip of the tail.…”

Section: Discussionmentioning

confidence: 99%

Hyperinsulinemic-euglycemic Clamps in Conscious, Unrestrained Mice

Ayala

Bracy

Malabanan

et al. 2011

JoVE

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106

101

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Type 2 diabetes is characterized by a defect in insulin action. The hyperinsulinemic-euglycemic clamp, or insulin clamp, is widely considered the "gold standard" method for assessing insulin action in vivo. During an insulin clamp, hyperinsulinemia is achieved by a constant insulin infusion. Euglycemia is maintained via a concomitant glucose infusion at a variable rate. This variable glucose infusion rate (GIR) is determined by measuring blood glucose at brief intervals throughout the experiment and adjusting the GIR accordingly. The GIR is indicative of whole-body insulin action, as mice with enhanced insulin action require a greater GIR. The insulin clamp can incorporate administration of isotopic 2[ 14 C]deoxyglucose to assess tissue-specific glucose uptake and [3-3 H]glucose to assess the ability of insulin to suppress the rate of endogenous glucose appearance (endoRa), a marker of hepatic glucose production, and to stimulate the rate of whole-body glucose disappearance (Rd).

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Section: Discussionmentioning

confidence: 99%

Hyperinsulinemic-euglycemic Clamps in Conscious, Unrestrained Mice

Ayala

Bracy

Malabanan

et al. 2011

JoVE

Self Cite

106

101

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“…For measurements of firstand second-phase insulin secretion, islets were incubated in 3 mM glucose KRB plus 30 mM KCl for 5 minutes, followed by incubation in 28 mM glucose KRB for an additional 10 minutes. Intracellular calcium measurements were made using the ratiometric calcium dye fura-2 (63). Islets were loaded with 3 μM fura-2-acetoxymethylester (fura-2 AM) for 30 minutes, transferred to a low-volume chamber (Warner Instruments), mounted on the stage of an Olympus BX51WI fluorescence microscope, and subsequently perifused with 3 mM followed by 28 mM glucose KRB delivered by a peristaltic pump (Gilson) maintained at 37°C with an in-line heater (Warner Instruments).…”

Section: Methodsmentioning

confidence: 99%

An intracellular role for ABCG1-mediated cholesterol transport in the regulated secretory pathway of mouse pancreatic β cells

Sturek¹,

Castle²,

Trace³

et al. 2010

J. Clin. Invest.

137

138

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Cholesterol is a critical component of cell membranes, and cellular cholesterol levels and distribution are tightly regulated in mammals. Recent evidence has revealed a critical role for pancreatic β cell-specific cholesterol homeostasis in insulin secretion as well as in β cell dysfunction in diabetes and the metabolic response to thiazolidinediones (TZDs), which are antidiabetic drugs. The ATP-binding cassette transporter G1 (ABCG1) has been shown to play a role in cholesterol efflux, but its role in β cells is currently unknown. In other cell types, ABCG1 expression is downregulated in diabetes and upregulated by TZDs. Here we have demonstrated an intracellular role for ABCG1 in β cells. Loss of ABCG1 expression impaired insulin secretion both in vivo and in vitro, but it had no effect on cellular cholesterol content or efflux. Subcellular localization studies showed the bulk of ABCG1 protein to be present in insulin granules. Loss of ABCG1 led to altered granule morphology and reduced granule cholesterol levels. Administration of exogenous cholesterol restored granule morphology and cholesterol content and rescued insulin secretion in ABCG1-deficient islets. These findings suggest that ABCG1 acts primarily to regulate subcellular cholesterol distribution in mouse β cells. Furthermore, islet ABCG1 expression was reduced in diabetic mice and restored by TZDs, implicating a role for regulation of islet ABCG1 expression in diabetes pathogenesis and treatment.

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“…This observation supports our previous findings regarding the importance of oscillations to normal islet health, 8,10 however, it should be noted that ideally oscillations should be recorded in steady-state glucose to prevent transient states in their oscillatory periods. 18,19 Two separate trials were conducted, one with untreated islets labeled with CTR and another with cytokine-treated islets labeled with CTR. In each trial, the cytokine-treated islets showed a substantially reduced GSCa regardless of labeling.…”

confidence: 99%