Insulin-Stimulated Glucose Transport and Insulin Internalization Share a Common Postbinding Step in Adipocytes

Jochen, Albert; Berhanu, Paulos

doi:10.2337/diab.36.4.542

Cited by 12 publications

(5 citation statements)

References 22 publications

(17 reference statements)

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“…A relationship between the biological activity of insulin and the internalization and intracellular processing of the insulinreceptor complex is suggested by various in vitro evidence (14)(15)(16)(17)(18)(19)(20)42). We observed multiple abnormalities of insulin and its receptor internalization and processing in insulinresistant states like obesity and NIDDM.…”

Section: Discussionmentioning

confidence: 95%

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Defects in Insulin-Receptor Internalization and Processing in Monocytes of Obese Subjects and Obese NIDDM Patients

et al. 1989

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We investigated intracellular processing of the insulin-receptor complex in monocytes from 12 healthy control subjects, 11 obese nondiabetic subjects, and 13 obese patients with non-insulin-dependent diabetes mellitus (NIDDM) by measuring receptor internalization, recovery of cell-surface insulin binding after receptor internalization, and the release of intracellular intact insulin (insulin retroendocytosis). When monocytes from the three groups of subjects were exposed to 100 nM unlabeled insulin for 30 min at 37 degrees C, the subsequent cell-surface 125I-labeled insulin binding was reduced, but the total number of insulin receptors, measured by radioimmunoassay, was not changed. These findings indicate a redistribution of insulin receptors from the surface to the cell interior. Insulin-receptor internalization was significantly lower in monocytes of obese NIDDM patients (mean +/- SE 17.8 +/- 4.7%) than in obese subjects and healthy control subjects (33.5 +/- 4.5%, P less than .05, and 34.4 +/- 3.7%, P less than .02, respectively). Moreover, in downregulated cells, a complete recovery of the initial insulin binding was observed in control subjects but not in obese NIDDM patients or obese nondiabetic subjects. The release of internalized insulin was also reduced in obese NIDDM patients and obese subjects (t 1/2 = 49.0 +/- 2.4 min, P less than .02; 47.4 +/- 5.7 min, P less than .05; and 32.9 +/- 3.8 in NIDDM patients, obese subjects, and control subjects, respectively). In the radioactivity released from monocytes of obese subjects and obese NIDDM patients, the percentage of intact insulin was higher (P less than .05) than in control subjects, suggesting reduced intracellular insulin degradation in obese subjects and obese NIDDM patients.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Discussionmentioning

confidence: 95%

“…These events involve the recycling and degradation of both insulin and its receptor (10)(11)(12)(13)(14) or their translocation to other intracellular organelles (7)(8)(9).. Past studies suggest that internalization (15)(16)(17)(18) and intracellular processing (19,20) of the insulin-receptor complex may be related to the hormone action.…”

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confidence: 99%

Defects in Insulin-Receptor Internalization and Processing in Monocytes of Obese Subjects and Obese NIDDM Patients

et al. 1989

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“…The first step in insulin clearance is binding to its receptor on the cell membrane activating the tyrosine kinase pathway leading to internalization of insulin followed by degradation in lysosomes . In vitro studies have indicated that insulin internalization and insulin action are linked . Thus insulin‐induced insulin receptor activation not only mediates insulin actions but is also involved in its clearance.…”

Section: Discussionmentioning

confidence: 99%

The early effect of sunitinib on insulin clearance in patients with metastatic renal cell carcinoma

Thijs

Tack

Graaf

et al. 2016

Brit J Clinical Pharma

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AIMSIn patients with diabetes treated with sunitinib symptomatic hypoglycaemia has been reported. To explore the mechanism of this adverse effect we performed a prospective study to investigate the effect of sunitinib on insulin concentration, insulin clearance and insulin sensitivity. METHODSWe studied the early effects of sunitinib on insulin sensitivity and insulin clearance with a hyperinsulinaemic euglycaemic clamp (insulin infusion rate 60 mU m À2 min À1 ; steady-state 90-120 min) in patients with renal cell carcinoma before and 1 week after the start of sunitinib 50 mg day À1 . Insulin sensitivity index (S I ) was defined as steady-state glucose disposal divided by the steady-state plasma insulin. RESULTSTen patients (one with diabetes, treated with metformin) were included in the study protocol. Steady-state insulin concentrations during the clamp increased after 1 week of sunitinib (from 128.9 ± 9.0 mU l À1 to 170.8 ± 12.8 mU l À1 , P < 0.05; 95% CI on difference À 64.3, À19.6). The calculated insulin sensitivity index decreased from 0.22 ± 0.04 before to 0.18 ± 0.02 μmol kg À1 min À1 per mU l À1 insulin (P < 0.05; 95% CI on difference 0.07, 0.08). As the insulin infusion rate was similar for both clamps, the increased steady-state insulin concentration indicates reduced insulin clearance.

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“…In contrast with the studies cited above, very rapid actions of insulin, such as stimulation of glucose transport, have been assumed to be exclusively mediated by the initial insulin-receptor interaction at the cell surface Haring et al, 1981) and to be independent of the lysosomal pathway. More recent reports in the literature, however, cast doubt on this assumption, suggesting a possible relationship between insulin processing and stimulation of glucose transport in isolated adipocytes (Frost & Lane, 1985;Jochen & Berhanu, 1987;Hashimoto et al, 1987).…”

Section: Introductionmentioning

confidence: 99%

Involvement of hormone processing in insulin-activated glucose transport by isolated cardiac myocytes

Eckel

Reinauer

1988

Biochemical Journal

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Isolated muscle cells from adult rat heart were used to study the relationship between myocardial insulin processing and insulin action on 3-O-methylglucose transport at 37 degrees C. Internalization of the hormone as measured by determination of the non-dissociable fraction of cell-bound insulin increased linearly up to 10 min, reaching a plateau by 30-60 min at 3 nM-insulin. At this hormone concentration the onset of insulin action was found to be biphasic, with a rapid phase up to 8 min, followed by a much slower phase, reaching maximal insulin action by 30-60 min. Insulin internalization was totally blocked by phenylarsine oxide, whereas dansylcadaverine had no effect on this process. Initial insulin action (5 min) on glucose transport was not affected by chloroquine and dansylcadaverine, but was completely abolished by treatment of cardiocytes with phenylarsine oxide. This drug effect was partly prevented by the presence of 2,3-dimercaptopropanol. Under steady-state conditions (60 min), the stimulatory action of insulin was decreased by about 60% by both chloroquine and dansylcadaverine. This study, demonstrates that insulin action on cardiac glucose transport is mediated by processing of the hormone. The data suggest dual pathways of insulin action involving initial processing of hormone-receptor complexes and lysosomal degradation.

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Insulin-Stimulated Glucose Transport and Insulin Internalization Share a Common Postbinding Step in Adipocytes

Cited by 12 publications

References 22 publications

Defects in Insulin-Receptor Internalization and Processing in Monocytes of Obese Subjects and Obese NIDDM Patients

Defects in Insulin-Receptor Internalization and Processing in Monocytes of Obese Subjects and Obese NIDDM Patients

The early effect of sunitinib on insulin clearance in patients with metastatic renal cell carcinoma

Involvement of hormone processing in insulin-activated glucose transport by isolated cardiac myocytes

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