Full Text Journal Articles by
Author Dennis Larkin

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Thyroid hormone synthesis continues despite biallelic thyroglobulin mutation with cell death.

Xiaohan Zhang, Aaron P Kellogg, Cintia E Citterio, Hao Zhang, Dennis Larkin, Yoshiaki Morishita, Héctor M Targovnik, Viviana A Balbi, Peter Arvan,

Complete absence of thyroid hormone is incompatible with life in vertebrates. Thyroxine is synthesized within thyroid follicles upon iodination of thyroglobulin conveyed from the endoplasmic reticulum (ER), via the Golgi complex, to the extracellular follicular lumen. In congenital hypothyroidism from biallelic thyroglobulin mutation, thyroglobulin is misfolded and cannot advance from ... Read more >>

JCI Insight (JCI insight)
[2021, 6(11):]

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Predisposition to Proinsulin Misfolding as a Genetic Risk to Diet-Induced Diabetes

Maroof Alam, Anoop Arunagiri, Leena Haataja, Mauricio Torres, Dennis Larkin, John Kappler, Niyun Jin, Peter Arvan,

Throughout evolution, proinsulin has exhibited significant sequence variation in both C-peptide and insulin moieties. As the proinsulin coding sequence evolves, the gene product continues to be under selection pressure both for ultimate insulin bioactivity and for the ability of proinsulin to be folded for export through the secretory pathway of ... Read more >>

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Cell death-associated lipid droplet protein CIDE-A is a noncanonical marker of endoplasmic reticulum stress.

Yoshiaki Morishita, Aaron P Kellogg, Dennis Larkin, Wei Chen, Suryakiran Vadrevu, Leslie Satin, Ming Liu, Peter Arvan,

Secretory protein misfolding has been linked to ER stress and cell death. We expressed a TGrdw transgene encoding TG-G(2298)R, a misfolded mutant thyroglobulin reported to be linked to thyroid cell death. When the TGrdw transgene was expressed at low level in thyrocytes of TGcog/cog mice that experienced severe ER stress, ... Read more >>

JCI Insight (JCI insight)
[2021, 6(7):]

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Role of Proinsulin Self-Association in Mutant INS gene-induced Diabetes of Youth

Jinhong Sun, Yi Xiong, Xin Li, Leena Haataja, Wei Chen, Saiful Mir, Rachel Madley, Dennis Larkin, Arfah Anjum, Balamurugan Dhayalan, Nischay Rege, Nalinda Wickramasinghe, Michael Weiss, Pamela Itkin-Ansari, Randal Kaufman, David Ostrov, Peter Arvan, Ming Liu,

Abnormal interactions between misfolded mutant and wild-type (WT) proinsulin in the endoplasmic reticulum (ER) drive the molecular pathogenesis of Mutant- INS -gene induced Diabetes of Youth (MIDY). How these abnormal interactions are initiated remains unknown. Normally, proinsulin-WT dimerizes in the ER. Here, we suggest that the normal proinsulin-proinsulin contact surface, ... Read more >>

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Monitoring C-Peptide Storage and Secretion in Islet β-Cells In Vitro and In Vivo.

Shuaishuai Zhu, Dennis Larkin, Shusheng Lu, Candice Inouye, Leena Haataja, Arfah Anjum, Robert Kennedy, David Castle, Peter Arvan,

Human proinsulin with C-peptide-bearing Superfolder Green Fluorescent Protein (CpepSfGFP) has been expressed in transgenic mice, driven by the Ins1 promoter. The protein, expressed exclusively in β-cells, is processed and stored as CpepSfGFP and human insulin comprising only ∼0.04% of total islet proinsulin plus insulin, exerting no metabolic impact. The kinetics ... Read more >>

Diabetes (Diabetes)
[2016, 65(3):699-709]

Cited: 22 times

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Impaired cleavage of preproinsulin signal peptide linked to autosomal-dominant diabetes.

Ming Liu, Roberto Lara-Lemus, Shu-ou Shan, Jordan Wright, Leena Haataja, Fabrizio Barbetti, Huan Guo, Dennis Larkin, Peter Arvan,

Recently, missense mutations upstream of preproinsulin's signal peptide (SP) cleavage site were reported to cause mutant INS gene-induced diabetes of youth (MIDY). Our objective was to understand the molecular pathogenesis using metabolic labeling and assays of proinsulin export and insulin and C-peptide production to examine the earliest events of insulin ... Read more >>

Diabetes (Diabetes)
[2012, 61(4):828-837]

Cited: 30 times

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In vivo misfolding of proinsulin below the threshold of frank diabetes.

Israel Hodish, Afaf Absood, Leanza Liu, Ming Liu, Leena Haataja, Dennis Larkin, Ahmed Al-Khafaji, Anthony Zaki, Peter Arvan,

<h4>Objective</h4>Endoplasmic reticulum (ER) stress has been described in pancreatic β-cells after onset of diabetes-a situation in which failing β-cells have exhausted available compensatory mechanisms. Herein we have compared two mouse models expressing equally small amounts of transgenic proinsulin in pancreatic β-cells.<h4>Research design and methods</h4>In hProCpepGFP mice, human proinsulin (tagged with ... Read more >>

Diabetes (Diabetes)
[2011, 60(8):2092-2101]

Cited: 27 times

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Misfolded proinsulin affects bystander proinsulin in neonatal diabetes.

Israel Hodish, Ming Liu, Gautam Rajpal, Dennis Larkin, Ronald W Holz, Aaron Adams, Leanza Liu, Peter Arvan,

It has previously been shown that misfolded mutant Akita proinsulin in the endoplasmic reticulum engages directly in protein complexes either with nonmutant proinsulin or with "hProCpepGFP" (human proinsulin bearing emerald-GFP within the C-peptide), impairing the trafficking of these "bystander" proinsulin molecules (Liu, M., Hodish, I., Rhodes, C. J., and Arvan, ... Read more >>

J Biol Chem (The Journal of biological chemistry)
[2010, 285(1):685-694]

Cited: 42 times

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Endoplasmic reticulum (ER) chaperone regulation and survival of cells compensating for deficiency in the ER stress response kinase, PERK.

Yukihiro Yamaguchi, Dennis Larkin, Roberto Lara-Lemus, Jose Ramos-Castañeda, Ming Liu, Peter Arvan,

The activity of PERK, an endoplasmic reticulum (ER) transmembrane protein kinase, assists in an ER stress response designed to inhibit general protein synthesis while allowing upregulated synthesis of selective proteins such as the ATF4 transcription factor. PERK null mice exhibit phenotypes that especially affect secretory cell types. Although embryonic fibroblasts ... Read more >>

J Biol Chem (The Journal of biological chemistry)
[2008, 283(25):17020-17029]

Cited: 30 times

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Protective effects of cyclooxygenase-2 gene inactivation against peripheral nerve dysfunction and intraepidermal nerve fiber loss in experimental diabetes.

Aaron P Kellogg, Tim D Wiggin, Dennis D Larkin, John M Hayes, Martin J Stevens, Rodica Pop-Busui,

<h4>Objective</h4>Activation of the cyclooxygenase (COX) pathway with secondary neurovascular deficits are implicated in the pathogenesis of experimental diabetic peripheral neuropathy (DPN). The aim of this study was to explore the interrelationships between hyperglycemia, activation of the COX-2 pathway, and oxidative stress and inflammation in mediating peripheral nerve dysfunction and whether ... Read more >>

Diabetes (Diabetes)
[2007, 56(12):2997-3005]

Cited: 61 times

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Regulation of the human taurine transporter by oxidative stress in retinal pigment epithelial cells stably transformed to overexpress aldose reductase.

Eitaro Nakashima, Rodica Pop-Busui, Roberto Towns, Thommey P Thomas, Yoshiuki Hosaka, Jiro Nakamura, Douglas A Greene, Paul D Killen, Justin Schroeder, Dennis D Larkin, Yuk Lam Ho, Martin J Stevens,

In diabetes, overexpression of aldose reductase (AR) and consequent glucose-induced impairment of antioxidant defense systems may predispose to oxidative stress and the development of diabetic complications, but the mechanisms are poorly understood. Taurine (2-aminoethanesulfonic acid) functions as an antioxidant, osmolyte, and calcium modulator such that its intracellular depletion could promote ... Read more >>

Antioxid Redox Signal (Antioxidants & redox signaling)
[2005, 7(11-12):1530-1542]

Cited: 22 times

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Taurine reverses neurological and neurovascular deficits in Zucker diabetic fatty rats.

Fei Li, Omorodola I Abatan, Howard Kim, Diana Burnett, Dennis Larkin, Irina G Obrosova, Martin J Stevens,

Increased oxidative stress is implicated in the pathogenesis of diabetic peripheral neuropathy (DPN). However, the efficacy of antioxidant therapy on DPN complicating type 2 diabetes remains unexplored. We therefore determined the ability of the antioxidant taurine to reverse deficits of hind limb sciatic motor and digital sensory nerve conduction velocity ... Read more >>

Neurobiol Dis (Neurobiology of disease)
[2006, 22(3):669-676]

Cited: 44 times

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Sympathetic dysfunction in type 1 diabetes: association with impaired myocardial blood flow reserve and diastolic dysfunction.

Rodica Pop-Busui, Ian Kirkwood, Helena Schmid, Victor Marinescu, Justin Schroeder, Dennis Larkin, Elina Yamada, David M Raffel, Martin J Stevens,

<h4>Objectives</h4>This study was designed to explore the relationships of early diabetic microangiopathy to alterations of cardiac sympathetic tone and myocardial blood flow (MBF) regulation in subjects with stable type 1 diabetes.<h4>Background</h4>In diabetes, augmented cardiac sympathetic tone and abnormal MBF regulation may predispose to myocardial injury and enhanced cardiac risk.<h4>Methods</h4>Subject groups ... Read more >>

J Am Coll Cardiol (Journal of the American College of Cardiology)
[2004, 44(12):2368-2374]

Cited: 87 times

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Taurine replacement attenuates hyperalgesia and abnormal calcium signaling in sensory neurons of STZ-D rats.

Fei Li, Irina G Obrosova, Omorodola Abatan, Dequan Tian, Dennis Larkin, Edward L Stuenkel, Martin J Stevens,

The etiology of painful diabetic neuropathy is poorly understood, but may result from neuronal hyperexcitability secondary to alterations of Ca2+ signaling in sensory neurons. The naturally occurring amino acid taurine functions as an osmolyte, antioxidant, Ca2+ modulator, inhibitory neurotransmitter, and analgesic such that its depletion in diabetes may predispose one ... Read more >>

Am J Physiol Endocrinol Metab (American journal of physiology. Endocrinology and metabolism)
[2005, 288(1):E29-36]

Cited: 61 times

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Establishment, maintenance, and transfection of in vitro cultures of human retinal pigment epithelium.

Martin J Stevens, Dennis D Larkin, Eva L Feldman, Monte A DelMonte, Douglas A Greene,

Methods Mol Med (Methods in molecular medicine)
[2005, 107:343-351]

Cited: 3 times

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All-trans retinoic acid improves structure and function of diabetic rat skin in organ culture.

James Varani, Patricia Perone, Matthew G Merfert, Sang Eun Moon, Dennis Larkin, Martin J Stevens,

Diabetes increases susceptibility to chronic ulceration. The cause of chronic wound formation in diabetic individuals is multifactorial but may be accelerated by changes in the structure and function of the skin secondary to impaired fibroblast proliferation, decreased collagen synthesis, and increased matrix metalloproteinase (MMP) expression. This study explored cellular and ... Read more >>

Diabetes (Diabetes)
[2002, 51(12):3510-3516]

Cited: 20 times

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Dissection of metabolic, vascular, and nerve conduction interrelationships in experimental diabetic neuropathy by cyclooxygenase inhibition and acetyl-L-carnitine administration.

Rodica Pop-Busui, Victor Marinescu, Carol Van Huysen, Fei Li, Kelli Sullivan, Douglas A Greene, Dennis Larkin, Martin J Stevens,

Alterations in cyclooxygenase (COX) pathway activity have been implicated in the pathogenesis of experimental diabetic neuropathy (EDN). These studies explore the relationships between COX-mediated and acetyl-L-carnitine (ALC)-sensitive defects that contribute to functional, metabolic, and vascular abnormalities of EDN. The effects of nonselective COX inhibition with flurbiprofen were contrasted with selective ... Read more >>

Diabetes (Diabetes)
[2002, 51(8):2619-2628]

Cited: 57 times

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