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  • 1
    In: Annals of Surgery, Ovid Technologies (Wolters Kluwer Health), Vol. 222, No. 4 ( 1995-10), p. 562-579
    Type of Medium: Online Resource
    ISSN: 0003-4932
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 1995
    detail.hit.zdb_id: 2002200-1
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  • 2
    In: Diabetes, American Diabetes Association, Vol. 46, No. 1 ( 1997-01-01), p. 28-33
    Abstract: The optimal site for pancreatic islet cell transplantation is presently unclear, although the liver has been the most commonly used. However, glucagon secretion from islets that have been autotransplanted in liver has been reported to be unresponsive to hypoglycemia yet responsive to arginine. To determine whether this selective glucagon secretory defect is related to the intrahepatic site of islet implantation or to the process of transplantation per se, we studied counterregulatory responses to hypoglycemia in dogs with pancreatic islet autotransplantation in the hepatic parenchyma (the intrahepatic [IH] group, n = 9) or the peritoneal cavity (the intraperitoneal [IP] group, n = 9), following total pancreatectomy, and compared them with the responses in normal controls (n = 10). Dogs were subjected to a hypoglycemic hyperinsulinemic (5 mU · kg−1 min−1) clamp for 90 min under general anesthesia. Arterial glucose concentrations were clamped at 2.7 mmol/l for the final 45 min of the clamp. Immediately following the clamp, glucagon responses to IV arginine (5 g) were also assessed. During hypoglycemia, glucagon responses in the IH group (maximal incremental glucagon = 33 ± 21 ng/l; glucagon area under curve [AUC] = 713 ± 1,022 ng · 1−1 · min−1) were significantly lower than either the IP (maximal incremental glucagon = 92 ± 32 ng/l; glucagon AUC = 4,090 ± 1,600 ng · 1−1 · min−1) or control (maximal incremental glucagon = 154 ± 71 ng/l; glucagon AUC = 6,943 ± 2,842 ng · 1−1 · min−1) group (IH vs. IP group, P & lt; 0.05; control vs. IH group, P & lt; 0.01). Glucagon responses in the IP group did not differ significantly from the control group. Epinephrine responses to hypoglycemia were similar in all groups, whereas neither of the transplanted groups (IH and IP) had pancreatic polypeptide responses. There was a prompt rise in plasma glucagon after intravenous arginine in all groups. These data indicate that glucagon unresponsiveness to hypoglycemia is specific to intrahepatically transplanted islets, rendering the liver a disadvantageous site for optimal α-cell function.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 1997
    detail.hit.zdb_id: 1501252-9
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  • 3
    Online Resource
    Online Resource
    Annual Reviews ; 1996
    In:  Annual Review of Medicine Vol. 47, No. 1 ( 1996-02), p. 69-83
    In: Annual Review of Medicine, Annual Reviews, Vol. 47, No. 1 ( 1996-02), p. 69-83
    Abstract: ▪ Abstract  Type-II (non-insulin-dependent) diabetes mellitus (NIDDM) is a heterogeneous disease resulting from insulin resistance and β-cell dysfunction. β-Cell dysfunction in Type-II diabetes is characterized by a specific lack of first-phase glucose-induced insulin secretion. This defect is readily reversible upon normalization of blood glucose levels. Chronic hyperglycemia itself is harmful to the β-cell and affects both insulin biosynthesis and exocytosis. No unique intracellular defect has been demonstrated to be responsible for all common forms of the disease. However, mutations of the glucokinase gene have been identified in maturity onset diabetes in the young, a particular form of NIDDM.
    Type of Medium: Online Resource
    ISSN: 0066-4219 , 1545-326X
    URL: Issue
    Language: English
    Publisher: Annual Reviews
    Publication Date: 1996
    detail.hit.zdb_id: 1481484-5
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  • 4
    Online Resource
    Online Resource
    Elsevier BV ; 1997
    In:  Endocrinology and Metabolism Clinics of North America Vol. 26, No. 3 ( 1997-9), p. 611-630
    In: Endocrinology and Metabolism Clinics of North America, Elsevier BV, Vol. 26, No. 3 ( 1997-9), p. 611-630
    Type of Medium: Online Resource
    ISSN: 0889-8529
    Language: English
    Publisher: Elsevier BV
    Publication Date: 1997
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  • 5
    In: Journal of Biological Chemistry, Elsevier BV, Vol. 271, No. 28 ( 1996-07), p. 16544-16552
    Type of Medium: Online Resource
    ISSN: 0021-9258
    Language: English
    Publisher: Elsevier BV
    Publication Date: 1996
    detail.hit.zdb_id: 2141744-1
    detail.hit.zdb_id: 1474604-9
    SSG: 12
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  • 6
    Online Resource
    Online Resource
    Informa UK Limited ; 1996
    In:  Postgraduate Medicine Vol. 99, No. 6 ( 1996-06), p. 143-152
    In: Postgraduate Medicine, Informa UK Limited, Vol. 99, No. 6 ( 1996-06), p. 143-152
    Type of Medium: Online Resource
    ISSN: 0032-5481 , 1941-9260
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 1996
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  • 7
    In: Diabetes, American Diabetes Association, Vol. 46, No. 2 ( 1997-02-01), p. 249-257
    Abstract: Impaired epinephrine secretion and symptom unawareness are characteristic of severe hypoglycemia in individuals with long-standing type I diabetes. Recently, the avoidance of clinical hypoglycemia has been reported to improve epinephrine and symptom responses to hypoglycemia in type I patients. However, the extent to which these defects can be restored in individuals with long-standing type I diabetes and autonomic neuropathy has not been assessed, nor has it been determined whether pancreas transplantation, which not only obviates hypoglycemia but also prevents hyperglycemia, results in the complete recovery of either epinephrine response or symptom awareness during insulin-induced hypoglycemia. We performed stepped hypoglycemic clamp studies in successful pancreas transplantation recipients to assess epinephrine and other counterregulatory hormone responses during hypoglycemia and to determine the degree to which hypoglycemic symptom recognition could be restored. Thirteen pancreas transplant recipients and matched control subjects were studied utilizing stepped hypoglycemic clamp protocol to achieve target glucose levels of 3.9, 3.3, 2.8, and 2.2 mmol/l (70, 60, 50, and 40 mg/dl, respectively). Plasma epinephrine response was significantly greater in healthy control subjects and pancreas transplant patients compared with type I subjects at the glucose plateaus of 3.9, 3.3, and 2.8 mmol/l. However, epinephrine response in pancreas transplant recipients was significantly less than that seen in either healthy control subjects or nondiabetic kidney transplant recipients at each of these glucose plateaus. The magnitude of the epinephrine response in pancreas transplant type I patients did not correlate with either the duration of diabetes, the duration of transplantation, or the measures of autonomic nerve function. Hypoglycemic symptom recognition was significantly greater in pancreas transplant subjects than type I patients and did not differ between pancreas transplant and control groups. No improvement in norepinephrine response was observed after pancreas transplantation, while glucagon responses to hypoglycemia were normalized in pancreas transplant patients. In conclusion, these studies uniquely demonstrate that successful pancreas transplantation improves epinephrine response and normalizes hypoglycemia symptom recognition in patients with long-standing diabetes and established autonomic neuropathy. No correlation was observed between the severity of autonomic neuropathy or the duration of diabetes and the recovery of either the epinephrine or symptom responses to hypoglycemia.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 1997
    detail.hit.zdb_id: 1501252-9
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  • 8
    Online Resource
    Online Resource
    Elsevier BV ; 1999
    In:  Endocrine Practice Vol. 5, No. 1 ( 1999-01), p. 24-28
    In: Endocrine Practice, Elsevier BV, Vol. 5, No. 1 ( 1999-01), p. 24-28
    Type of Medium: Online Resource
    ISSN: 1530-891X
    Language: English
    Publisher: Elsevier BV
    Publication Date: 1999
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  • 9
    Online Resource
    Online Resource
    American Diabetes Association ; 1997
    In:  Diabetes Vol. 46, No. 1 ( 1997-01-01), p. 23-27
    In: Diabetes, American Diabetes Association, Vol. 46, No. 1 ( 1997-01-01), p. 23-27
    Abstract: Defective glucagon secretion during hypoglycemia is characteristic of long-standing type I diabetes. To determine whether this defect can be corrected by successful intrahepatic islet transplantation, we performed studies of hypoglycemia in four nondiabetic patients with chronic pancreatitis who had undergone total pancreatectomy and successful intrahepatic islet autotransplantation, in two type I diabetic recipients of successful intrahepatic islet allotransplantation, and in matched control subjects. We examined 1) whether intrahepatic islet autotransplantation provides glucagon secretion during prolonged periods of hypoglycemia and 2) whether intrahepatic islet allotransplantation in type I diabetic patients and consequent long-term normoglycemia reestablishes native α-cell responses to hypoglycemia. Glucagon secretion was assessed during 3-h hypoglycemic hyperinsulinemic clamp studies. The islet autograft recipients were studied 63 ± 19 months posttransplant, and all were insulinindependent and normoglycemic (HbA1c, 5.8 ±± 0.2%). Neither allograft recipient required exogenous insulin and maintained HbA1c levels of 5.7 and 6.4% 30 and 34 months posttransplant, respectively. All recipients were normoglycemic (fasting glucose: autograft recipients, 5.6 ± 0.1 mmol/l; allograft recipient #1, 6.3 mmol/l; allograft recipient #2, 5.8 mmol/l) at the time of study. During hypoglycemia, no increase in glucagon secretion was observed in either the auto- or allotransplant recipients, whereas healthy control subjects and recipients of kidney transplantation had significant increases in glucagon. In contrast, both allo- and autograft recipients had glucagon responses to intravenous arginine. These data uniquely demonstrate that: 1) intrahepatic islet transplant grafts secrete glucagon in response to arginine, but fail to secrete glucagon in response to sustained hypoglycemia; and 2) the restoration of sustained normoglycemia for over 2 years in type I diabetic patients may not reestablish glucagon responses from the native pancreas during hypoglycemia. Transplantation sites other than the liver may be required to achieve normal glucagon secretion from the transplanted islets.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 1997
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  • 10
    In: Diabetes, American Diabetes Association, Vol. 47, No. 1 ( 1998-01-01), p. 113-118
    Abstract: IDDM patients treated with conventional subcutaneous insulin have an abnormal increase in cholesteryl ester transfer (CET), the proatherogenic step in reverse-cholesterol transport that results in the enrichment of the apolipoprotein (apo) B-containing lipoproteins (VLDL, LDL) with cholesteryl ester (CE). This disturbance is closely linked to iatrogenic hyperinsulinemia and the nonphysiologic stimulation of lipoprotein lipase (LpL), a physiologic activator of CET, because lowering systemic insulin levels by administering insulin through the intraperitoneal insulin route normalizes LpL and CET. Hyperinsulinemia persists in IDDM patients who undergo successful pancreas-kidney transplantation (PKT) when their allografts are placed in the pelvis and drain into the iliac vein. Therefore, to determine whether hyperinsulinemia promotes CET in this setting, we studied CET, LpL, and insulin levels in 14 euglycemic normolipidemic IDDM PKT patients with nearnormal kidney function (creatinine 1.5 ± 0.4 mg/dl). Consistent with our prediction, the net mass of CE transferred from HDL to VLDL + LDL was significantly increased in the PKT group (P & lt; 0.001) compared with nondiabetic renal transplant patients receiving the same immunosuppressive drugs and healthy control subjects. Both basal and arginine-stimulated insulin levels were increased above the kidney transplant group's levels and correlated with the mass of CE transferred at 2 h (r = 0.71, P & lt; 0.05; r = 0.66, P & lt; 0.05, respectively). Total basal LpL activities, LpL and hepatic triacylglycerol lipase activities, and LpL mass all tended to be higher than levels in healthy control subjects. Consistent with these changes in lipase activity, VLDL particle size was significantly reduced (P & lt; 0.025) compared with that of control subjects. These findings indicate that PKT patients with systemically draining allografts have a persisting profile of potentially atherogenic disturbances in insulin levels, LpL, and CET that resemble IDDM patients treated with conventional subcutaneous insulin injections.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 1998
    detail.hit.zdb_id: 1501252-9
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