Restoration of Glucose Counterregulation by Islet Transplantation in Long-standing Type 1 Diabetes.

Abstract:

:Patients with long-standing type 1 diabetes (T1D) may exhibit defective glucose counterregulation and impaired hypoglycemia symptom recognition that substantially increase their risk for experiencing severe hypoglycemia. The purpose of this study was to determine whether intrahepatic islet transplantation improves endogenous glucose production (EGP) in response to hypoglycemia in T1D patients experiencing severe hypoglycemia. We studied longitudinally subjects (n = 12) with ∼30 years, disease duration before and 6 months after intrahepatic islet transplantation using stepped hyperinsulinemic-hypoglycemic and paired hyperinsulinemic-euglycemic clamps with infusion of 6,6-(2)H2-glucose and compared the results with those from a nondiabetic control group (n = 8). After islet transplantation, HbA1c was normalized, and time spent while hypoglycemic (<70 mg/dL) was nearly abolished as indicated by continuous glucose monitoring. In response to insulin-induced hypoglycemia, C-peptide (absent before transplant) was appropriately suppressed, glucagon secretion was recovered, and epinephrine secretion was improved after transplantation. Corresponding to these hormonal changes, the EGP response to insulin-induced hypoglycemia, which was previously absent, was normalized after transplantation, with a similar effect seen for autonomic symptoms. Because the ability to increase EGP is ultimately required to circumvent the development of hypoglycemia, these results provide evidence that intrahepatic islet transplantation can restore glucose counterregulation in long-standing T1D and support its consideration as treatment for patients with hypoglycemia unawareness experiencing severe hypoglycemia.

journal_name

Diabetes

journal_title

Diabetes

authors

Rickels MR,Fuller C,Dalton-Bakes C,Markmann E,Palanjian M,Cullison K,Tiao J,Kapoor S,Liu C,Naji A,Teff KL

doi

10.2337/db14-1620

subject

Has Abstract

pub_date

2015-05-01 00:00:00

pages

1713-8

issue

5

eissn

0012-1797

issn

1939-327X

pii

db14-1620

journal_volume

64

pub_type

临床试验,杂志文章

相关文献

DIABETES文献大全
  • New alpha 2-adrenergic blocker (DG-5128) improves insulin secretion and in vivo glucose disposal in NIDDM patients.

    abstract::Effects of oral administration of DG-5128, a new oral hypoglycemic agent, on glycemic control after a mixed meal and an in vivo glucose disposal were measured in subjects with nonobese non-insulin-dependent diabetes mellitus (NIDDM). Oral administration of DG-5128 significantly (P less than .05) enhanced insulin secre...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.35.10.1085

    authors: Kashiwagi A,Harano Y,Suzuki M,Kojima H,Harada M,Nishio Y,Shigeta Y

    更新日期:1986-10-01 00:00:00

  • Use of UW solution in pancreas transplantation.

    abstract::We have recently reported successful 72-h preservation of the canine pancreas with a new cold-storage solution developed at the University of Wisconsin (UW solution). Over 10 mo, we performed 11 combined pancreas-kidney and 4 isolated-pancreas transplants with this solution. In situ cooling of the donor pancreas was p...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.38.1.s7

    authors: D'Alessandro AM,Stratta RJ,Sollinger HW,Kalayoglu M,Pirsch JD,Belzer FO

    更新日期:1989-01-01 00:00:00

  • Growth hormone overexpression in the central nervous system results in hyperphagia-induced obesity associated with insulin resistance and dyslipidemia.

    abstract::It is well known that peripherally administered growth hormone (GH) results in decreased body fat mass. However, GH-deficient patients increase their food intake when substituted with GH, suggesting that GH also has an appetite stimulating effect. Transgenic mice with an overexpression of bovine GH in the central nerv...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.54.1.51

    authors: Bohlooly-Y M,Olsson B,Bruder CE,Lindén D,Sjögren K,Bjursell M,Egecioglu E,Svensson L,Brodin P,Waterton JC,Isaksson OG,Sundler F,Ahrén B,Ohlsson C,Oscarsson J,Törnell J

    更新日期:2005-01-01 00:00:00

  • The Mammalian target of rapamycin pathway regulates nutrient-sensitive glucose uptake in man.

    abstract::The nutrient-sensitive kinase mammalian target of rapamycin (mTOR) and its downstream target S6 kinase (S6K) are involved in amino acid-induced insulin resistance. Whether the mTOR/S6K pathway directly modulates glucose metabolism in humans is unknown. We studied 11 healthy men (29 years old, BMI 23 kg/m(2)) twice in ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db06-1016

    authors: Krebs M,Brunmair B,Brehm A,Artwohl M,Szendroedi J,Nowotny P,Roth E,Fürnsinn C,Promintzer M,Anderwald C,Bischof M,Roden M

    更新日期:2007-06-01 00:00:00

  • Visualization of the insulin receptor by immunoblotting.

    abstract::Insulin receptors from rat hepatoma cells (Fao) and human placenta were partially purified by detergent solubilization and lectin purification. The insulin receptor preparations were subjected to sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis under reducing or nonreducing conditions. The proteins were...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.33.10.923

    authors: Maron R,Kahn CR,Jacobs S,Fujita-Yamaguchi Y

    更新日期:1984-10-01 00:00:00

  • Sphingosine kinase activity and sphingosine-1 phosphate production in rat pancreatic islets and INS-1 cells: response to cytokines.

    abstract::Sphingosine-1 phosphate (S1P) is a bioactive sphingolipid with the potential to mobilize Ca2+, to inhibit apoptosis, and to promote mitogenesis. Sphingosine kinase (SPHK) and S1P were characterized in INS-1 insulinoma cells and isolated rat islets of Langerhans. SPHK activity increased in INS-1 cell homogenates treate...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.54.5.1429

    authors: Mastrandrea LD,Sessanna SM,Laychock SG

    更新日期:2005-05-01 00:00:00

  • Impaired insulin-induced platelet antiaggregating effect in obesity and in obese NIDDM patients.

    abstract::To investigate the effects of insulin on platelets in obesity and in non-insulin-dependent diabetes mellitus (NIDDM)--classic insulin-resistant states--we determined ADP-induced platelet aggregation and platelet cGMP (guanosine 3',5'-cyclic monophosphate) content in platelet-rich plasma obtained from nine obese subjec...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.44.11.1318

    authors: Trovati M,Mularoni EM,Burzacca S,Ponziani MC,Massucco P,Mattiello L,Piretto V,Cavalot F,Anfossi G

    更新日期:1995-11-01 00:00:00

  • Developmental Programming of Obesity and Diabetes in Mouse, Monkey, and Man in 2018: Where Are We Headed?

    abstract::Childhood obesity and its comorbidities continue to accelerate across the globe. Two-thirds of pregnant women are obese/overweight, as are 20% of preschoolers. Gestational diabetes mellitus (GDM) is escalating, affecting up to 1 in 5 pregnant women. The field of developmental origins of health and disease has begun to...

    journal_title:Diabetes

    pub_type: 杂志文章,评审

    doi:10.2337/dbi17-0011

    authors: Friedman JE

    更新日期:2018-11-01 00:00:00

  • Reestablishment of Glucose Inhibition of Glucagon Secretion in Small Pseudoislets.

    abstract::Misregulated hormone secretion from the islet of Langerhans is central to the pathophysiology of diabetes. Although insulin plays a key role in glucose regulation, the importance of glucagon is increasingly acknowledged. However, the mechanisms that regulate glucagon secretion from α-cells are still unclear. We used p...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db16-1291

    authors: Reissaus CA,Piston DW

    更新日期:2017-04-01 00:00:00

  • Glycoprotein-like large glucagon immunoreactive species in extracts of the fetal bovine pancreas.

    abstract::Large glucagon immunoreactive substances, extracted from the fetal bovine pancreas and separated by gel filtration in the presence of 6 M guanidinium-hydrochloride, were submitted to lectin-sepharose affinity column chromatograph. Gel-filtered peak I (approximately 45 K delta) and peak II (approximately 10 K delta) in...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diacare.31.11.1002

    authors: Tung AK,Cockburn E,Siu KP

    更新日期:1982-11-01 00:00:00

  • Central role for interleukin-2 in type 1 diabetes.

    abstract::Type 1 diabetes presents clinically with overt hyperglycemia resulting from progressive immune-mediated destruction of pancreatic β-cells and associated metabolic dysfunction. Combined genetic and immunological studies now highlight deficiencies in both the interleukin-2 (IL-2) receptor and its downstream signaling pa...

    journal_title:Diabetes

    pub_type: 杂志文章,评审

    doi:10.2337/db11-1213

    authors: Hulme MA,Wasserfall CH,Atkinson MA,Brusko TM

    更新日期:2012-01-01 00:00:00

  • Radioassay determination of insulin autoantibodies in NOD mice. Correlation with increased risk of progression to overt diabetes.

    abstract::In an initial cross-sectional study, 29 female and 25 male nondiabetic weaned nonobese diabetic (NOD) mice of various ages (age range 30-300 days, mean 108 +/- 10 days) and 11 unweaned NOD pups were evaluated for competitive insulin autoantibodies (CIAAs) with a fluid-phase radioassay. Eleven of 54 (20%) weaned NOD mi...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.38.3.358

    authors: Ziegler AG,Vardi P,Ricker AT,Hattori M,Soeldner JS,Eisenbarth GS

    更新日期:1989-03-01 00:00:00

  • Inflammation and endothelial activation is evident at birth in offspring of mothers with type 1 diabetes.

    abstract:OBJECTIVE:Offspring of mothers with diabetes are at risk of obesity and glucose intolerance in later life. In adults, markers of subclinical inflammation (C-reactive protein [CRP] and interleukin [IL]-6) and endothelial activation (intracellular adhesion molecule [ICAM]-1) are associated with obesity and higher risk fo...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db07-0662

    authors: Nelson SM,Sattar N,Freeman DJ,Walker JD,Lindsay RS

    更新日期:2007-11-01 00:00:00

  • Calcium-calmodulin-dependent myosin phosphorylation by pancreatic islets.

    abstract::Pancreatic islets contain enzyme activity which catalyzes the phosphorylation by MgATP of cardiac, skeletal, or smooth muscle myosin light chains. The enzyme is activated by calcium (Ka = 10 microM) and calmodulin (Ka = 2 nM) and inhibited by trifluoperazine (Ki = 10 microM), a known inhibitor of calmodulin and of ins...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.31.6.566

    authors: MacDonald MJ,Kowluru A

    更新日期:1982-06-01 00:00:00

  • 6-Phosphogluconate/glucose-6-phosphate ratio in rat pancreatic islets during inhibition of insulin release by exogenous insulin.

    abstract::Inhibition of glucose-stimulated insulin release by exogenous insulin has been demonstrated in pancreatic islets to be associated with a decrease of the NADPH/NADP ratio and the pentose-phosphate cycle activity. Batches of five islets were incubated for 15 and 90 minutes in 1 ml. of KRB buffer with 2 per cent albumin ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.26.9.857

    authors: Akhtar MS,Verspohl E,Hegner D,Ammon HP

    更新日期:1977-09-01 00:00:00

  • Octreotide prevents the early increase in renal insulin-like growth factor binding protein 1 in streptozotocin diabetic rats.

    abstract::The early renal growth in streptozotocin (STZ)-induced diabetic rats is preceded by a transient rise in renal tissue insulin-like growth factor (IGF)-I concentration. Administration of the long-acting somatostatin analog octreotide to STZ diabetic rats inhibits the early increase in kidney IGF-I and the increase in ki...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.47.6.924

    authors: Raz I,Rubinger D,Popovtzer M,Grønbaek H,Weiss O,Flyvbjerg A

    更新日期:1998-06-01 00:00:00

  • Insulin resistance caused by massive degradation of subcutaneous insulin.

    abstract::Severe resistance to subcutaneous insulin but sensitivity to intravenous insulin persisted for 15 months in a 17-year-old diabetic girl. Heat-labile insulin-degrading activity was present in the patient's ketotic sera and in the 100,000 g fraction (soluble fraction) of adipose tissue. Serum-degrading activity was not ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.28.7.640

    authors: Paulsen EP,Courtney JW 3rd,Duckworth WC

    更新日期:1979-07-01 00:00:00

  • Pharmacological vasodilation improves insulin-stimulated muscle protein anabolism but not glucose utilization in older adults.

    abstract:OBJECTIVE:Skeletal muscle protein metabolism is resistant to the anabolic action of insulin in healthy, nondiabetic older adults. This defect is associated with impaired insulin-induced vasodilation and mTORC1 signaling. We hypothesized that, in older subjects, pharmacological restoration of insulin-induced capillary r...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db10-0415

    authors: Timmerman KL,Lee JL,Fujita S,Dhanani S,Dreyer HC,Fry CS,Drummond MJ,Sheffield-Moore M,Rasmussen BB,Volpi E

    更新日期:2010-11-01 00:00:00

  • Adverse effects of dietary glycotoxins on wound healing in genetically diabetic mice.

    abstract::Advanced glycoxidation end products (AGEs) are implicated in delayed diabetic wound healing. To test the role of diet-derived AGE on the rate of wound healing, we placed female db/db (+/+) (n = 55, 12 weeks old) and age-matched control db/db (+/-) mice (n = 45) on two diets that differed only in AGE content (high [H-A...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.52.11.2805

    authors: Peppa M,Brem H,Ehrlich P,Zhang JG,Cai W,Li Z,Croitoru A,Thung S,Vlassara H

    更新日期:2003-11-01 00:00:00

  • Sodium-Glucose Cotransporter 2 Inhibitors: A Case Study in Translational Research.

    abstract::Sodium-glucose cotransporter 2 (SGLT2) inhibitors are the most recently approved class of diabetes drugs. Unlike other agents, SGLT2 inhibitors act on the kidney to promote urinary glucose excretion. SGLT2 inhibitors provide multiple benefits, including decreased HbA1c, body weight, and blood pressure. These drugs hav...

    journal_title:Diabetes

    pub_type: 杂志文章,评审

    doi:10.2337/dbi18-0006

    authors: Beitelshees AL,Leslie BR,Taylor SI

    更新日期:2019-06-01 00:00:00

  • Intra-abdominal fat is a major determinant of the National Cholesterol Education Program Adult Treatment Panel III criteria for the metabolic syndrome.

    abstract::The underlying pathophysiology of the metabolic syndrome is the subject of debate, with both insulin resistance and obesity considered as important factors. We evaluated the differential effects of insulin resistance and central body fat distribution in determining the metabolic syndrome as defined by the National Cho...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.53.8.2087

    authors: Carr DB,Utzschneider KM,Hull RL,Kodama K,Retzlaff BM,Brunzell JD,Shofer JB,Fish BE,Knopp RH,Kahn SE

    更新日期:2004-08-01 00:00:00

  • A genome-wide linkage scan for genes controlling variation in renal function estimated by serum cystatin C levels in extended families with type 2 diabetes.

    abstract::We performed a variance components linkage analysis of renal function, measured as glomerular filtration rate (GFR), in 63 extended families with multiple members with type 2 diabetes. GFR was estimated from serum concentrations of cystatin C and creatinine in 406 diabetic and 428 nondiabetic relatives. Results for cy...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db06-0781

    authors: Placha G,Poznik GD,Dunn J,Smiles A,Krolewski B,Glew T,Puppala S,Schneider J,Rogus JJ,Rich SS,Duggirala R,Warram JH,Krolewski AS

    更新日期:2006-12-01 00:00:00

  • Analysis of parent-offspring trios provides evidence for linkage and association between the insulin gene and type 2 diabetes mediated exclusively through paternally transmitted class III variable number tandem repeat alleles.

    abstract::Variation at the variable number tandem repeat (VNTR) minisatellite 5' of the insulin gene (INS) is associated with several phenotypes, including type 1 diabetes, polycystic ovary syndrome, and birth weight. Case-control studies have suggested that class III VNTR alleles are also associated with type 2 diabetes, but r...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.49.1.126

    authors: Huxtable SJ,Saker PJ,Haddad L,Walker M,Frayling TM,Levy JC,Hitman GA,O'Rahilly S,Hattersley AT,McCarthy MI

    更新日期:2000-01-01 00:00:00

  • Glycogen synthesis in human gastrocnemius muscle is not representative of whole-body muscle glycogen synthesis.

    abstract::The introduction of 13C magnetic resonance spectroscopy (MRS) has enabled noninvasive measurement of muscle glycogen synthesis in humans. Conclusions based on measurements by the MRS technique assume that glucose metabolism in gastrocnemius muscle is representative for all skeletal muscles and thus can be extrapolated...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.54.5.1277

    authors: Serlie MJ,de Haan JH,Tack CJ,Verberne HJ,Ackermans MT,Heerschap A,Sauerwein HP

    更新日期:2005-05-01 00:00:00

  • Nutrient stress activates inflammation and reduces glucose metabolism by suppressing AMP-activated protein kinase in the heart.

    abstract:OBJECTIVE:Heart failure is a major cause of mortality in diabetes and may be causally associated with altered metabolism. Recent reports indicate a role of inflammation in peripheral insulin resistance, but the impact of inflammation on cardiac metabolism is unknown. We investigated the effects of diet-induced obesity ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db08-1361

    authors: Ko HJ,Zhang Z,Jung DY,Jun JY,Ma Z,Jones KE,Chan SY,Kim JK

    更新日期:2009-11-01 00:00:00

  • Inhibition of Soluble Epoxide Hydrolase 2 Ameliorates Diabetic Keratopathy and Impaired Wound Healing in Mouse Corneas.

    abstract::EPHX2 (encoding soluble epoxide hydrolase [sEH]) converts biologically active epoxyeicosatrienoic acids (EETs), anti-inflammatory and profibrinolytic effectors, into the less biologically active metabolites, dihydroxyeicostrienoic acids. We sought to characterize the expression and the function of EPHX2 in diabetic co...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db17-1336

    authors: Sun H,Lee P,Yan C,Gao N,Wang J,Fan X,Yu FS

    更新日期:2018-06-01 00:00:00

  • Effect of two amino acids in TM17 of Sulfonylurea receptor SUR1 on the binding of ATP-sensitive K+ channel modulators.

    abstract::The sulfonylurea receptor (SUR) is the important regulatory subunit of ATP-sensitive K+ channels. It is an ATP-binding cassette protein comprising 17 transmembrane helices. SUR is endowed with binding sites for channel blockers like the antidiabetic sulfonylurea glibenclamide and for the chemically very heterogeneous ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.53.suppl_3.s128

    authors: Hambrock A,Kayar T,Stumpp D,Osswald H

    更新日期:2004-12-01 00:00:00

  • PPARδ activation protects endothelial function in diabetic mice.

    abstract::Recent evidence highlights the therapeutic potential of peroxisome proliferator-activated receptor-δ (PPARδ) agonists to increase insulin sensitivity in diabetes. However, the role of PPARδ in regulating vascular function is incompletely characterized. We investigate whether PPARδ activation improves endothelial funct...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db12-0117

    authors: Tian XY,Wong WT,Wang N,Lu Y,Cheang WS,Liu J,Liu L,Liu Y,Lee SS,Chen ZY,Cooke JP,Yao X,Huang Y

    更新日期:2012-12-01 00:00:00

  • Minimal effects of phorbol esters on glucose transport and insulin sensitivity of rat skeletal muscle.

    abstract::Protein kinase C (PKC) has been suggested as a mediator of insulin's effect on glucose transport, and PKC-mediated modulation of tyrosine kinase activity in the insulin receptor has been implicated in regulating the insulin sensitivity of tissues. Because skeletal muscle is a major target of insulin action, we examine...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.37.5.499

    authors: Sowell MO,Treutelaar MK,Burant CF,Buse MG

    更新日期:1988-05-01 00:00:00

  • Lack of glucagon response to hypoglycemia in type I diabetics after long-term optimal therapy with a continuous subcutaneous insulin infusion pump.

    abstract::Counterregulatory hormonal responses were studied in six patients after 4-18 mo treatment with a continuous subcutaneous insulin infusion pump. In response to insulin-induced hypoglycemia, significant increases in epinephrine, norepinephrine, cortisol, and growth hormone were measured in all subjects, while in five of...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.32.5.398

    authors: Bergenstal RM,Polonsky KS,Pons G,Jaspan JB,Rubenstein AH

    更新日期:1983-05-01 00:00:00