Gordon C. Weir
Harvard University
Publications 386
#1Gordon C. Weir (Harvard University)H-Index: 85
#2Jason L. Gaglia (Harvard University)H-Index: 13
Last.Susan Bonner-Weir (Harvard University)H-Index: 96
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Summary For patients with type 1 diabetes, it is accepted among the scientific community that there is a marked reduction in β-cell mass; however, with type 2 diabetes, there is disagreement as to whether this reduction in mass occurs in every case. Some have argued that β-cell mass in some patients with type 2 diabetes is normal and that the cause of the hyperglycaemia in these patients is a functional abnormality of insulin secretion. In this Personal View, we argue that a deficient β-cell mas...
#1Gordon C. Weir (Harvard University)H-Index: 85
Reduction of β-cell mass and function is central to the pathogenesis of type 2 diabetes. The terms glucotoxicity, lipotoxicity, and glucolipotoxicity are used to describe potentially responsible processes. The premise is that chronically elevated glucose levels are toxic to β-cells, that elevated lipid levels in the form of circulating free fatty acids (FFA) also have toxic effects, and that the combination of the two, glucolipotoxicity, is particularly harmful. Much work has shown that high con...
3 CitationsSource
#1Shady Farah (MIT: Massachusetts Institute of Technology)H-Index: 12
#2Joshua C. DoloffH-Index: 16
Last.Dana Z. AndersonH-Index: 103
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Implantable medical devices have revolutionized modern medicine. However, immune-mediated foreign body response (FBR) to the materials of these devices can limit their function or even induce failure. Here we describe long-term controlled-release formulations for local anti-inflammatory release through the development of compact, solvent-free crystals. The compact lattice structure of these crystals allows for very slow, surface dissolution and high drug density. These formulations suppress FBR ...
4 CitationsSource
#1Cristina Aguayo-Mazzucato (Harvard University)H-Index: 13
#2Joshua Andle (Harvard University)H-Index: 1
Last.Susan Bonner-Weir (Harvard University)H-Index: 96
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Summary Type 2 diabetes (T2D) is an age-related disease. Although changes in function and proliferation of aged β cells resemble those preceding the development of diabetes, the contribution of β cell aging and senescence remains unclear. We generated a β cell senescence signature and found that insulin resistance accelerates β cell senescence leading to loss of function and cellular identity and worsening metabolic profile. Senolysis (removal of senescent cells), using either a transgenic INK-A...
5 CitationsSource
#1Abir Zainal (UR: University of Rochester)
#2Andrew L. Dunn (URMC: University of Rochester Medical Center)
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#1Yoav Evron (Beta)H-Index: 5
#2Clark K. Colton (MIT: Massachusetts Institute of Technology)H-Index: 52
Last.Avi Rotem (Beta)H-Index: 12
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Transplantation of encapsulated islets can cure diabetes without immunosuppression, but oxygen supply limitations can cause failure. We investigated a retrievable macroencapsulation device wherein islets are encapsulated in a planar alginate slab and supplied with exogenous oxygen from a replenishable gas chamber. Translation to clinically-useful devices entails reduction of device size by increasing islet surface density, which requires increased gas chamber pO2. Here we show that islet surface...
10 CitationsSource
#2Omid VeisehH-Index: 37
Last.Jose Oberholzer (UIC: University of Illinois at Chicago)H-Index: 50
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The transplantation of pancreatic islet cells could restore glycaemic control in patients with type 1 diabetes. Microspheres for islet encapsulation have enabled long-term glycaemic control in rodent models of diabetes; however, humans transplanted with equivalent microsphere formulations have experienced only transient islet graft function owing to a vigorous foreign-body response (FBR), to pericapsular fibrotic overgrowth (PFO) and, in upright bipedal species, to the sedimentation of the micro...
20 CitationsSource
#1Ahmed I. MahmoudH-Index: 12
Last.Richard T. LeeH-Index: 100
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#1Gordon C. Weir (Harvard University)H-Index: 85
#2Mario R. EhlersH-Index: 12
Last.Terry B. Strom (BIDMC: Beth Israel Deaconess Medical Center)H-Index: 46
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4 CitationsSource
#1Albert Hwa (Joslin Diabetes Center)H-Index: 6
#2Gordon C. Weir (Joslin Diabetes Center)H-Index: 85
Purpose of Review There is considerable interest in using macroencapsulation devices as a delivery strategy for transplanting insulin-producing cells. This review aims to summarize recent advances, to highlight remaining challenges, and to provide recommendations for the field.
8 CitationsSource