A protocol for studying glucose homeostasis and islet function in mice

Rijjal, Dana Al; Wheeler, Michael B.

doi:10.1016/j.xpro.2022.101171

Cited by 12 publications

(7 citation statements)

References 3 publications

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“…Furthermore, such increased in vitro insulin secretion induction indices are often reported when compared to in vivo. [21,51] TRPC3 appears to accomplish the primary function in insulin secretion since there was no additive impact of the non-selective TRPCs inhibitor, SKF96365, compared to Pyr10. However, prior research found that TRPC3 was present in rat islets and INS-1E cell line but the TRPC1 and ORAI1 channels were the predominant K ATP -independent channels, ruling out TRPC3 as a candidate based on TRPC3 blockage with Pyr3 and knockdown by a dominant-negative expression.…”

Section: Discussionmentioning

confidence: 99%

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TRPC3 Regulates Islet Beta‐Cell Insulin Secretion

et al. 2023

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Insulin release is tightly controlled by glucose-stimulated calcium (GSCa) through hitherto equivocal pathways. This study investigates TRPC3, a non-selective cation channel, as a critical regulator of insulin secretion and glucose control. TRPC3's involvement in glucose-stimulated insulin secretion (GSIS) is studied in human and animal islets. TRPC3-dependent in vivo insulin secretion is investigated using pharmacological tools and Trpc3 −/− mice. TRPC3's involvement in islet glucose uptake and GSCa is explored using fluorescent glucose analogue 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-D-glucose and calcium imaging. TRPC3 modulation by a small-molecule activator, GSK1702934A, is evaluated in type 2 diabetic mice. TRPC3 is functionally expressed in human and mouse islet beta cells. TRPC3-controlled insulin secretion is K ATP -independent and primarily mediated by diacylglycerol channel regulation of the cytosolic calcium oscillations following glucose stimulation. Conversely, glucose uptake in islets is independent of TRPC3. TRPC3 pharmacologic inhibition and knockout in mice lead to defective insulin secretion and glucose intolerance. Subsequently, TRPC3 activation through targeted small-molecule enhances insulin secretion and alleviates diabetes hallmarks in animals. This study imputes a function for TRPC3 at the onset of GSIS. These insights strengthen one's knowledge of insulin secretion physiology and set forth the TRPC3 channel as an appealing candidate for drug development in the treatment of diabetes.

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Section: Discussionmentioning

confidence: 99%

“…Furthermore, such increased in vitro insulin secretion induction indices are often reported when compared to in vivo. [ 21,51 ]…”

Section: Discussionmentioning

confidence: 99%

TRPC3 Regulates Islet Beta‐Cell Insulin Secretion

et al. 2023

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“…Blood glucose was measured using an Accu-Chek Performa glucose monitor (Roche Diagnostics, Castle Hill, Australia). Plasma insulin was measured using ELISA (Crystal Chem, Downers Grove, IL) 34 .…”

Section: Methodsmentioning

confidence: 99%

Chronic intermittent fasting impairs β-cell maturation and function in adolescent mice

Matta,

Weber,

Erener

et al. 2024

Preprint

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Intermittent fasting (IF) is a nutritional lifestyle intervention with broad metabolic benefits, but whether the impact of IF depends on the individual's age is unclear. Here, we investigated the effects of IF on systemic metabolism and pancreatic islet function in old, middle-aged, and young mice. Short-term IF improved glucose homeostasis across all age groups, without altering islet function and morphology. In contrast, while chronic IF was beneficial for adult mice, it resulted in impaired β-cell function in the young. Using scRNAseq, we delineated that the β-cell maturation and function score were reduced in young mice. In human islets, a similar pattern was observed in Type 1 (T1D), but not in Type 2 diabetes (T2D), suggesting that the impact of chronic IF in adolescence is linked to the development of β-cell dysfunction. Our study suggests considering the duration of IF in younger people, as it may enhance rather than reduce diabetes outcomes.

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“…A glucose tolerance test (GTT) was conducted in the fifth week. The mice were fasted for 16 h and injected intraperitoneally with 1.5 g/kg.bw glucose (50-99-7, Sigma-Aldrich Co., Ltd.) [ [29] , [30] , [31] ]. The blood glucose level of each mouse was measured at 0 min, 15 min, 30 min, 45 min, 60 min, and 120 min after the injection.…”

Section: Methodsmentioning

confidence: 99%